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Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD)., Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD., Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18 F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended., Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment., Competing Interests: Declaration of Competing Interest Dr. van Laarhoven reports a consultant or advisory role: Amphera, Anocca, Astellas, AstraZeneca, Beigene, Boehringer, Daiichy-Sankyo, Dragonfly, MSD, Myeloid, Servier; Research funding, medication supply, and/or other research support: Auristone, Incyte, Merck, ORCA, Servier; Speaker role: Astellas, Beigene, Benecke, BMS, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Springer, Travel Congress Management B.V. Dr. Muijs reports institutional grants from: Elekta, IBA, RaySearch, Siemens, Mirada, Bergoz Instrumentation and Medical Data Works, KWF, all outside the submitted work. Dr. van Hillegersberg has a consulting and advisory role at Intuitive Surgical, Medtronic, Olympus and J&J Ethicon. Dr. de Manzoni reports personal fees from Lilly, outside the submitted work. Dr. Gani reports travel grants from Elekta and departmental research cooperation, outside the submitted work. Dr. Smyth is supported by the NIHR Biomedical Research Centre at Oxford (the views expressed in this Article are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health) and resports personal fees/grants from: Astra Zeneca, Beigene, BMS, Amal Therapeutics, Amgen, Daiichi Sankyo, Merck, Servier, Novartis, Pfizer, Roche, and Zymeworks, all outside the submitted work. Dr. Haj Mohammad reports consulation fees from: Merck, BMS, Eli Lilly, Astra Zeneca, and research funding from Servier, all outside the submitted work. Dr. Adenis reports grants and personal fees from Bayer, personal fees and non-financial support from MSD, personal fees from: BMS, Novartis, Pierre-Fabre, non-financial support from Servier, grants from Sanofi, all outside the submitted work. Dr. Lordick reports grants from: BMS and Gilead, personal fees from: Amgen, Astellas, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Elsevier, Incyte, Merck, MSD, Roche, Servier, all outside the submitted work. Dr. Slingerland reports an advisory role at BMS and Lilly. Dr. van Berge Henegouwen received researcher-initiated grant from Stryker and is consultant for Alesi Surgical, Johnson and Johnson, Medtronic, BBraun and Viatris. Dr Nilsson reports advisory roles for BMS and Medtronic. Dr. Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc; and also educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). Dr. Tabernero declares institutional financial interest in form of financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK. Dr. Nieuwenhuijzen reports advisory/speaker roles from Medtronic and Lilly. All remaining authors have declared no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose/objective: Chemo-radiotherapy can improve the oncological outcome of esophageal cancer (EC) patients, but may cause long term radiation-induced toxicity, including an increased risk of non-cancer related death. For lung cancer patients, a model to predict 2-year total mortality using mean heart dose (MHD) and gross tumor volume (GTV) has previously been developed and validated. This project aimed to externally validate this model in EC patients., Methods: Five EC patient cohorts from 3 different Dutch centres were used for model validation. External validity of the model was assessed separately in definitive (n = 170) and neo-adjuvant (n = 568) chemoradiotherapy (dCRT and nCRT) patients. External validity was assessed in terms of calibration by calibration plots, calibration-in-the-large (CITL) and calibration slope (CS), and discrimination by assessment of the c-statistic. If suboptimal model performance was observed, the model was further updated accordingly., Results: For the dCRT patients, good calibration was found after adjustment of the intercept (CITL 0.00; CS 1.08). The c-statistic of the adjusted model was 0.67 (95%CI: 0.58 to 0.75). For nCRT patients the model needed adjustment of both the slope and the intercept because of initial miscalibration in the validation population (CITL 0.00; CS 1.72). After recalibration, the model showed perfect calibration (i.e., CITL 0, CS 1), as is common after recalibration. The c-statistic of the recalibrated model equaled 0.62 (95%CI: 0.57 to 0.67)., Conclusion: The existing model for 2-year mortality prediction in lung cancer patients, based on the predictive factors MHD and GTV, showed good performance in EC patients after updating the intercept and/or slope of the original model., Competing Interests: Declaration of competing interest 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., (Copyright © 2023. Published by Elsevier B.V.)

Background: Multidisciplinary team meetings (MDTM) and especially MDTMs in which expert centres are involved (expert MDTMs) are a key element in adequate cancer care. However, variation among hospitals in the proportion of patients presented during an expert MDTM has been described. This study aims to investigate national practice variation in the proportion of patients with oesophageal or gastric cancer being discussed during an expert MDTM., Methods: Patients diagnosed with oesophageal or gastric cancer in 2018-2019 were selected from the Netherlands Cancer Registry (n = 6,921). Multilevel logistic regression analyses were used to analyse the association between patient, and tumour characteristics, and the probability to be discussed in an expert MDTM. Variation was analysed according to the hospital and region of diagnosis for: all patients, patients with a potentially curable (cT1-4A cTX, any cN, cM0) or incurable tumour stage (cT4b and/or cM1)., Results: In total, 79% of patients were discussed during an expert MDTM, of whom 84% (n = 3,424) and 71% (n = 2,018) with potentially curable, or incurable oesophageal or gastric cancer, respectively. The proportion of patients discussed during an expert MDTM ranged from 54% to 98%, and 17% to 100% between hospitals for potentially curable and incurable patients, respectively (all p < 0.0001). Adjusted analyses showed significant hospital (all p < 0.0001), but no regional variation regarding the patients discussed during an expert MDTM., Conclusion: For patients with oesophageal or gastric cancer the probability of being discussed during an expert MDTM varies considerably according to the hospital of diagnosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Local treatment improves the outcomes for oligometastatic disease (OMD, i.e. an intermediate state between locoregional and widespread disseminated disease). However, consensus about the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer is lacking. The aim of this study was to develop a multidisciplinary European consensus statement on the definition, diagnosis and treatment of oligometastatic oesophagogastric cancer., Methods: In total, 65 specialists in the multidisciplinary treatment for oesophagogastric cancer from 49 expert centres across 16 European countries were requested to participate in this Delphi study. The consensus finding process consisted of a starting meeting, 2 online Delphi questionnaire rounds and an online consensus meeting. Input for Delphi questionnaires consisted of (1) a systematic review on definitions of oligometastatic oesophagogastric cancer and (2) a discussion of real-life clinical cases by multidisciplinary teams. Experts were asked to score each statement on a 5-point Likert scale. The agreement was scored to be either absent/poor (<50%), fair (50%-75%) or consensus (≥75%)., Results: A total of 48 experts participated in the starting meeting, both Delphi rounds, and the consensus meeting (overall response rate: 71%). OMD was considered in patients with metastatic oesophagogastric cancer limited to 1 organ with ≤3 metastases or 1 extra-regional lymph node station (consensus). In addition, OMD was considered in patients without progression at restaging after systemic therapy (consensus). For patients with synchronous or metachronous OMD with a disease-free interval ≤2 years, systemic therapy followed by restaging to consider local treatment was considered as treatment (consensus). For metachronous OMD with a disease-free interval >2 years, either upfront local treatment or systemic treatment followed by restaging was considered as treatment (fair agreement)., Conclusion: The OMEC project has resulted in a multidisciplinary European consensus statement for the definition, diagnosis and treatment of oligometastatic oesophagogastric adenocarcinoma and squamous cell cancer. This can be used to standardise inclusion criteria for future clinical trials., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. van Laarhoven reports grants or advisory/speaker role from: Astellas, BMS, Dragonfly, Lilly, Merck, Novartis, Nordic Pharma, Servier; research funding or medical supply from: Bayer, BMS, Celgene, Janssen, Incyte, Lilly, Merck, Nordic Pharma, Philips, Roche, Servier; and has received unrestricted research funding (non-commercial) from: Dutch Cancer Society, NWO/ZonMw, European Research Council, MaagLeverDarm Stichting. Dr. Muijs reports institutional grants from: Elekta, IBA, RaySearch, Siemens, Mirada, Bergoz Instrumentation and Medical Data Works, KWF, all outside the submitted work. Dr. van Hillegersberg has a consulting and advisory role at Intuitive Surgical. Dr. de Manzoni reports personal fees from Lilly, outside the submitted work. Dr. Gani reports travel grants from Elekta and departmental research cooperation, outside the submitted work. Dr. Smyth reports personal fees/grants from: Astra Zeneca, Beigene, BMS, Amal Therapeutics, Amgen, Daiichi Sankyo, Merck, Servier, Novartis, Pfizer, Roche, and Zymeworks, all outside the submitted work. Dr. Haj Mohammad reports consulation fees from: Merck, BMS, Eli Lilly, Astra Zeneca, and research funding from Servier, all outside the submitted work. Dr. Adenis reports grants and personal fees from Bayer, personal fees and non-fianciel support from MSD, personal fees from: BMS, Novartis, Pierre-Fabre, non-financial support from Servier, grants from Sanofi, all outside the submitted work. Dr. Lordick reports grants from: BMS and Gilead, personal fees from: Amgen, Astellas, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Elsevier, Incyte, Merck, MSD, Roche, Servier, all outside the submitted work. Dr. Slingerland reports an advisory role at BMS and Lilly. Dr. van Berge Henegouwen received researcher-initiated grant from Stryker and is consultant for Alesi Surgical, Johnson and Johnson, Medtronic, Braun and Mylan. Dr Nilsson reports advisory roles for BMS and Medtronic. All remaining authors have declared no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Respiratory-induced motion of oesophageal tumours and lymph nodes can influence positron-emission tomography/computed tomography (PET/CT). The aim was to compare standard three-dimensional (3D) and motion-compensated PET/CT regarding standardized uptake value (SUV), metabolic tumour volume (MTV) and detection of lymph node metastases., Methods: This prospective observational study (NCT02424864) included 37 newly diagnosed oesophageal cancer patients. Diagnostic PET/CT was reconstructed in 3D and motion-compensated PET/CT. MTVs of the primary tumour were calculated using an automated region-growing algorithm with SUV thresholds of 2.5 (MTV2.5) and ≥ 50% of SUVmax (MTV50%). Blinded for reconstruction method, a nuclear medicine physician assessed all lymph nodes showing 18 F‑fluorodeoxyglucose uptake for their degree of suspicion., Results: The mean (95% CI) SUVmax of the primary tumour was 13.1 (10.6-15.5) versus 13.0 (10.4-15.6) for 3D and motion-compensated PET/CT, respectively. MTVs were also similar between the two techniques. Bland-Altman analysis showed mean differences between both measurements (95% limits of agreement) of 0.08 (-3.60-3.75), -0.26 (-2.34-1.82), 4.66 (-29.61-38.92) cm 3 and -0.95 (-19.9-18.0) cm 3 for tumour SUVmax, lymph node SUVmax, MTV2.5 and MTV50%, respectively. Lymph nodes were classified as highly suspicious (30/34 nodes), suspicious (20/22) and dubious (66/59) for metastases on 3D/motion-compensated PET/CT. No additional lymph node metastases were found on motion-compensated PET/CT. SUVmax of the most intense lymph nodes was similar for both scans: mean (95% CI) 6.6 (4.3-8.8) and 6.8 (4.5-9.1) for 3D and motion-compensated, respectively., Conclusion: SUVmax of the primary oesophageal tumour and lymph nodes was comparable on 3D and motion-compensated PET/CT. The use of motion-compensated PET/CT did not improve lymph node detection., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer., Materials and Methods: Patients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses., Results: In 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8-61.5 months), 58% (95% CI 48-66), and 49% (95% CI 40-57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31-48), and 45% (95% CI 36-54). Three- and five-year risk of LRR were 26% (95% CI 19-33), and 30% (95% CI 22-38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached)., Conclusion: In patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years., Competing Interests: Declaration of competing interest JV has served as a consultant for AstraZeneca, MSD, Pierre Fabre, and Servier, and has received institutional research funding from Servier. All outside the submitted work. SG has received institutional research funding from Roche, Pfizer, Novartis, and Eli Lilly. All outside the submitted work. CM had research collaborations with IBA, Siemens, Raystation, and Mirada. All outside the submitted work. VT has received honoraria/travel grants from Roche, Novartis, Pfizer, Lilly, and Accord Healthcare, and has received institutional research funding from AstraZeneca, Roche, Pfizer, Novartis, Eisai, and Lilly. All outside the submitted work. The other authors have declared no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: Determining prognosis following poor response to neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma (OAC) remains challenging. An immunosuppressive tumour microenvironment (TME) as well as immune infiltrate density and composition are considered to play a critical role in the immune interaction between host and tumour and can predict therapy response and survival in many cancers, including gastrointestinal malignancies. The aim of this study was to establish the TME characteristics associated with survival following a poor response to nCRT., Methods and Results: The prognostic significance of OAC-associated CD3 + , CD4 + , CD8 + , forkhead box protein 3 (FoxP3 + ) and programmed cell death ligand 1 (PD-L1) expression was studied by immunohistochemistry and quantified by automated image analysis in 123 patients who underwent nCRT and curative resection. Results from good and poor responders were contrasted and immune infiltration was related to disease course in both groups. Subsequently a cohort of 57 patients with a moderate response to nCRT was analysed in a similar fashion. Tumour cell percentage positively correlated to immune infiltration markers. In good and moderate responders, none of the immune infiltrate parameters was associated with survival; in poor responders CD8 + was an independent negative predictor of OS in univariate analysis (P = 0.03) and high CD8 + infiltration was associated with worse OS (15 versus 32 months, P = 0.042)., Conclusion: A high CD8 + density is an independent biomarker of poor OS in poor responders to nCRT, but not in good and moderate responders. Our results suggest that patients with a poor response to nCRT but concomitant high CD8 + counts in the resection specimen require adjuvant therapy., (© 2021 John Wiley & Sons Ltd.)

Oncology care is increasingly a multidisciplinary endeavour, and radiation therapy continues to have a key role across the disease spectrum in nearly every cancer. However, the field of radiation oncology is still one of the most poorly understood of the cancer disciplines. In this Review, we attempt to summarise and contextualise developments within the field of radiation oncology for the non-radiation oncologist. We discuss advancements in treatment technologies and imaging, followed by an overview of the interplay with advancements in systemic therapy and surgical techniques. Finally, we review new frontiers in radiation oncology, including advances within the metastatic disease continuum, reirradiation, and emerging types of radiation therapy., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: In about 30% of patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgical resection for locally advanced oesophageal cancer no vital tumour is found in the resection specimen. Accurate clinical response assessment is critical if deferral from surgery is considered in complete responders. Our study aimed to compare the performance of MRI and of FDG-PET/CT for the detection of residual disease after nCRT., Methods: Patients with oesophageal cancer eligible for nCRT and oesophagectomy were prospectively included. All patients underwent FDG-PET/CT and MRI before and between 6 and 8 weeks after nCRT. Two radiologists scored the MRI scans, and two nuclear medicine physicians scored the FDG-PET/CT scans using a 5-point score for residual disease. Histopathology after oesophagectomy represented the reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated for detection of residual tumour (ypT+), residual nodal disease (ypN+), and any residual disease (ypT+Nx/ypT0N+)., Results: Seven out of 33 (21%) patients had a pathological complete response. The AUCs for individual readers to detect ypT+ were 0.71/0.70 on diffusion-weighted (DW)-MRI and 0.54/0.57 on FDG-PET/CT, and to detect ypN+ were 0.89/0.81 on DW-MRI and 0.75/0.71 on FDG-PET/CT. The AUCs/sensitivities/specificities for the individual readers to detect any residual disease were 0.74/92%/57% and 0.70/96%/43% on MRI; these were 0.49/69%/29% and 0.60/69%/43% on FDG-PET/CT, respectively., Conclusion: MRI reached higher diagnostic accuracies than FDG-PET/CT for the detection of residual tumour in oesophageal cancer patients at 6 to 8 weeks after nCRT.

Background: Proximal esophageal cancer (EC) is commonly treated with definitive chemoradiation (CRT). The radiation dose and type of chemotherapy backbone are still under debate. The objective of this study was to compare the treatment outcomes of contemporary CRT regimens. Material and Methods: In this retrospective observational cohort study, we included patients with locally advanced squamous cell cancer of the proximal esophagus, from 11 centers in the Netherlands, treated with definitive CRT between 2004 and 2014. Each center had a preferential CRT regimen, based on cisplatin (Cis) or carboplatin-paclitaxel (CP) combined with low (≤50.4 Gy) or high (>50.4 Gy) dose radiotherapy (RT). Differences in overall survival (OS) between CRT regimens were assessed using a fully adjusted Cox proportional hazards and propensity score (PS) weighted model. Safety profiles were compared using a multilevel logistic regression model. Results: Two hundred patients were included. Fifty-four, 39, 95, and 12 patients were treated with Cis-low-dose RT, Cis-high-dose RT, CP-low-dose RT, and CP-high-dose RT, respectively. Median follow-up was 62.6 months (95% CI: 47.9-77.2 months). Median OS (21.9 months; 95% CI: 16.9-27.0 months) was comparable between treatment groups (logrank p  = .88), confirmed in the fully adjusted and PS weighted model ( p  > .05). Grades 3-5 acute adverse events were less frequent in patients treated with CP-low-dose RT versus Cis-high-dose RT (OR 3.78; 95% CI: 1.31-10.87; p  = .01). The occurrence of grades 3-5 late toxicities was not different between treatment groups. Conclusion: Our study was unable to demonstrate a difference in OS between the CRT regimens, probably related to the relatively small sample size. Based on the superior safety profile, carboplatin and paclitaxel-based CRT regimens are preferred in patients with locally advanced proximal EC.

Objectives: In order to select oesophageal cancer patients after neoadjuvant chemoradiotherapy (nCRT) for organ-preserving treatment instead of surgery, a high diagnostic accuracy is required. The aim of this study was to evaluate whether MRI had additional value to gastroscopy with biopsies and endosonographic ultrasound (EUS) with fine needle aspiration (FNA) for the detection of residual tumour after nCRT., Methods: Twenty-two patients with oesophageal cancer eligible for nCRT followed by oesophagectomy were prospectively included. All patients underwent (T2- and diffusion-weighted) MRI and gastroscopy+EUS before and after nCRT. Histopathology after oesophagectomy was the reference standard with pathological complete response (pCR) defined as ypT0N0. Diagnostic performance regarding the detection of residual tumour was calculated for gastroscopic biopsies and for EUS-FNA without and with MRI., Results: Nineteen of the 22 patients (86%) did not achieve pCR after nCRT (7 ypT+N+, 11 ypT+N0, 1 ypT0N+). Biopsies detected residual tumour in 6 of 18 ypT+ patients. After adding MRI, 16 of 18 residual tumours were assessed correctly. EUS-FNA detected 3 out of 8 ypN+ patients, while MRI did not improve detection. Overall, adding MRI improved sensitivity for detection of residual tumour to 89% (17 of 19) from 47% (9 of 19) with endoscopic biopsies and EUS-FNA only., Conclusion: In this small study, the detection of residual tumour after nCRT in oesophageal cancer patients was improved by the addition of MRI to gastroscopy and EUS., Key Points: • In this small study, the detection of residual tumour after neoadjuvant chemoradiotherapy in oesophageal cancer patients was improved by adding MRI including diffusion-weighted images to gastroscopy and endosonographic ultrasound. • With the addition of MRI assessment to gastroscopy and endosonographic ultrasound, the considerable risk of missing residual tumours decreased from 53 to 11%, while the pitfall was overstaging in one out of three complete responders.

Purpose: Accurate preoperative prediction of pathologic response to neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal cancer could enable omission of esophagectomy in patients with a pathologic complete response (pCR). This study aimed to evaluate the individual and combined value of 18 F-fluorodeoxyglucose positron emission tomography with integrated computed tomography ( 18 F-FDG PET/CT) and diffusion-weighted magnetic resonance imaging (DW-MRI) during and after nCRT to predict pathologic response in patients with esophageal cancer., Methods and Materials: In this multicenter prospective study, patients scheduled to receive nCRT followed by esophagectomy for esophageal cancer underwent 18 F-FDG PET/CT and DW-MRI scanning before the start of nCRT, during nCRT, and before esophagectomy. Response to nCRT was based on histopathologic evaluation of the resection specimen. Relative changes in 18 F-FDG PET/CT and DW-MRI parameters were compared between patients with pCR and non-pCR groups. Multivariable ridge regression analyses with bootstrapped c-indices were performed to evaluate the individual and combined value of 18 F-FDG PET/CT and DW-MRI., Results: pCR was found in 26.1% of 69 patients. Relative changes in 18 F-FDG PET/CT parameters after nCRT (Δ standardized uptake value [SUV] mean,post P = .016, and Δ total lesion glycolysis post P = .024), as well as changes in DW-MRI parameters during nCRT (Δ apparent diffusion coefficient [ADC] during P = .008) were significantly different between pCR and non-pCR. A c-statistic of 0.84 was obtained for a model with ΔADC during , ΔSUV mean,post , and histology in classifying patients as pCR (versus 0.82 for ΔADC during and 0.79 for ΔSUV mean,post alone)., Conclusions: Changes on 18 F-FDG PET/CT after nCRT and early changes on DW-MRI during nCRT can help identify pCR to nCRT in esophageal cancer. Moreover, 18 F-FDG PET/CT and DW-MRI might be of complementary value in the assessment of pCR., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To accurately quantify esophageal tumor position variability and to optimize image guided correction strategies., Material and Methods: Esophageal cancer patients receiving chemoradiotherapy (41.4-50.4 Gy in 23-28 fractions combined with carboplatin plus paclitaxel) were included in a prospective cohort study (NCT02139488). Gold fiducial markers were inserted into the esophageal tumors during diagnostic endoscopic ultrasound. Four-dimensional (4D) planning computed tomography (CT) and daily 4D cone beam (CB) CT scans were acquired. Each CBCT was registered to the planning CT using different regions of interest (bone; 3D), and carina, diaphragm, clinical target volume (CTV), and fiducial markers (4D) for alignment and using the fiducial markers as the true tumor position. Subsequently, a planning target volume (PTV) margin accounting for residual uncertainties, including the average respiratory motion, was calculated for each of these registrations., Results: Fifty-six patients with tumors located in the proximal (n = 1), mid (n = 7), or distal esophagus (n = 25) or at the gastroesophageal junction (n = 23) were included. The average peak-to-peak respiratory tumor motion was 0.20, 0.92, and 0.34 cm on the planning CT in left-right (LR), cranial-caudal (CC), and anterior-posterior (AP) directions, respectively. The required PTV margin with average motion amplitude, depending on the correction strategy used for image guidance, ranged from 0.8 cm to 1.0 cm, 1.1 cm to 1.6 cm, and 0.7 cm to 0.9 cm in LR, CC, and AP direction, respectively. A registration based on the CTV resulted in the smallest PTV margins (0.8, 1.1, and 0.7 cm in LR, CC, and AP direction, respectively). For bone registration the calculated PTV margins were 1.0, 1.3, and 0.7 cm in LR, CC, and AP directions, respectively. The registration based on the diaphragm increased PTV margins., Conclusions: Substantial and anisotropic position variability of esophageal tumors was observed during radiation therapy, and nonuniform margins should be considered. Cranial-caudal PTV margins need to be larger than those commonly used. Target positioning during image-guided radiotherapy could be improved with a CTV registration-based correction strategy., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim was to perform a systematic review on the value of diffusion-weighted MRI (DW-MRI) with apparent diffusion coefficient (ADC) mapping in the prediction and assessment of response to chemo- and/or radiotherapy in oesophageal cancer., Materials and Methods: A systematic search was performed on Pubmed, Embase, Medline and Cochrane databases. Studies that evaluated the ADC for response evaluation before, during or after chemo- and/or radiotherapy were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess the quality of the included studies., Results: Fourteen studies, comprising 516 patients, in which the response to treatment in oesophageal cancer was evaluated on ADC maps were included. Acquisition parameter settings for DW-MRI and ROI placement varied substantially. The reference standard was RECIST or endoscopic assessment in eight non-surgery studies and histopathology after surgery in six studies. A high pre-treatment ADC significantly correlated with good response in three out of 12 studies; conversely, one study reported a significantly higher pre-treatment ADC in poor responders. In five out of eight studies good responders showed a significantly larger relative increase in ADC two weeks after the onset of treatment (range 23-59%) than poor responders (range 1.5-17%). After chemo- and/or radiotherapy ADC results varied considerably, amongst others due to large variation in the interval between completion of therapy and DW-MRI., Conclusion: DW-MRI for response evaluation to chemo- and/or radiotherapy in oesophageal cancer shows variable methods and results. A large relative ADC increase after two weeks of treatment seems most predictive for good response., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To assess the technical feasibility of injection, visibility on imaging modalities, and positional stability of a novel liquid fiducial marker (ie, BioXmark) for radiation therapy in patients with esophageal cancer., Methods: First, the visibility on imaging of different volumes of the liquid marker was analyzed ex vivo in porcine tissue (ie, on computed tomography [CT], cone beam CT (CBCT), and magnetic resonance imaging [MRI]). Next, for the in vivo part, the liquid fiducial markers were injected under endoscopic (ultrasound) guidance in 10 patients with curable esophageal cancer. The technical feasibility of the injection procedure and the clinical performance (ie, visibility and positional stability on imaging) were evaluated. Planning CT, daily CBCT, and serial MRI images (before, during, and after chemoradiation therapy in a subset of 3 patients) were acquired., Results: Ex vivo, the optimal volume for good visibility without artifacts was 0.1 mL per injected marker. In vivo, a total of 28 markers were injected in 10 patients (range, 0.025-0.1 mL). No adverse effects were identified. The first 2 cases (4 markers) were considered as learning cases. A total of 19 of 24 of the liquid markers (79%) were visible on CT, 3 of 4 (75%) on MRI, and 19 of 24 (79%) on the first CBCT. All markers with an injected volume of >0.05 mL were visible on the different imaging modalities. Positional stability analysis on CBCT identified no time trend during the radiation therapy course. No artifacts could be detected for liquid marker volumes of 0.05 and 0.025 mL in CT or CBCT., Conclusions: Injection of a liquid fiducial marker for esophageal cancer radiation therapy is technically feasible with no adverse events identified. Volumes of >0.05 mL have an appropriate visibility on CT, CBCT, and MRI, with an excellent positional stability. Liquid fiducial markers are therefore promising for use in image guided radiation therapy., (Copyright © 2019 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Current delineation of the gross tumor volume (GTV) in esophageal cancer relies on computed tomography (CT) and combination with 18 F-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., (© 2019 The Authors.)

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., (© 2019 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Introduction: Chemoradiotherapy and surgery are the basis of the potentially curative treatment for esophageal cancer. Approximately 1 in 5 patients, however, do not benefit from this intensive treatment due to early treatment failure. The aim of this study was to evaluate levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 at diagnosis, in relation to survival and early treatment failure (disease recurrence or death within 1 year after surgery)., Methods: Patients with esophageal adenocarcinoma scheduled for chemoradiotherapy followed by surgery between 1998 and 2014 were selected from a retrospectively collected database if both CEA and CA19-9 levels were measured before the start of treatment., Results: Pretreatment CEA and CA19-9 levels were known in 102 patients. Median overall survival differed (P<0.001) between patients with normal levels of both CEA and CA19-9 (n=59; 51 mo), patients with elevated CEA only (n=13; 43 mo), patients with elevated CA19-9 only (n=19; 24 mo), and those with elevated levels of both CEA and CA19-9 (n=11; 11 mo). Elevation of both CEA and CA19-9 was associated with early treatment failure (odds ratio: 10.4; 95% confidence interval: 2.4-45.5, P=0.002). Median time to tumor recurrence was 34 months in patients with normal CEA and CA19-9 levels, and 7 months in those with elevated levels of both (P=0.003)., Conclusions: Pretreatment elevated CEA and CA19-9 levels were significantly associated with early treatment failure and decreased overall survival in this esophageal adenocarcinoma patient cohort treated with curative intent. Until prospective validation, CEA and CA19-9 might play a role in identifying high-risk patients before the start of intensive locoregional therapy.

Background and Purpose: Accurate 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 Methods: Twenty 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., Results: After 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., Conclusion: In 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.

Background: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18 F-fluorodeoxyglucose positron emission tomography with computed tomography ( 18 F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR., Methods: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18 F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival., Discussion: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped., Trial Registration: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under ClinicalTrials.gov Identifier: NCT03474341 .

Objectives: The objective of this study is to compare long-term outcomes between younger and older (70 y and above) esophageal cancer patients treated with curative intent., Materials and Methods: Overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free interval were compared between older (70 y and above) and younger (below 70 y) esophageal cancer patients treated between 1998 and 2013. Treatment consisted of neoadjuvant chemoradiotherapy with surgery or definitive chemoradiotherapy: 36 to 50.4 Gy in 18 to 28 fractions combined with 5-fluorouracil/cisplatin or carboplatin/paclitaxel., Results: The study comprised 253 patients, of whom 76 were 70 years and older. Median age was 64 years (range, 41 to 83). Most patients had stage II-IIIA disease (83%). Planned treatment was neoadjuvant chemoradiotherapy with surgery for 169 patients (41 patients aged 70 y and older) and definitive chemoradiotherapy for 84 patients (31 patients aged 70 y and older). The compliance to radiotherapy was 92%, with no difference between older and younger patients. In 33 patients (13 patients aged 70 y and older) planned surgery was not performed. Median follow-up was 4.9 years. Three-year OS was 42%. The multivariable analysis showed no statistical difference in OS or in DFS comparing older and younger patients: OS (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.61-1.28), DFS (HR, 0.87; 95% CI, 0.60-1.25). Elderly showed a longer locoregional recurrence-free interval; HR, 0.53 (95% CI, 0.30-0.92; P=0.02) and a higher pathologic complete response rate (50% vs. 25%; P=0.02)., Conclusions: Long-term outcomes of older esophageal cancer patients (70 y and above) selected for treatment with neoadjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy were comparable with the outcomes of their younger counterparts. Advanced age alone should not be a contraindication for potentially curative chemoradiotherapy-based treatment in esophageal cancer patients.

Purpose: To explore the potential benefit and complementary value of a multiparametric approach using diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) for prediction of response to neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer., Material and Methods: Forty-five patients underwent both DW-MRI and DCE-MRI prior to nCRT (pre), during nCRT (week 2-3) (per) and after completion of nCRT, but prior to esophagectomy (post). Subsequently, histopathologic tumor regression grade (TRG) was assessed. Tumor apparent diffusion coefficient (ADC) and area-under-the-concentration time curve (AUC) were calculated for DW-MRI and DCE-MRI, respectively. The ability of these parameters to predict pathologic complete response (pCR, TRG1) or good response (GR, TRG ≤ 2) to nCRT was assessed. Furthermore the complementary value of DW-MRI and DCE-MRI was investigated., Results: GR was found in 22 (49%) patients, of which 10 (22%) patients showed pCR. For DW-MRI, the 75th percentile (P75) ΔADC post-pre was most predictive for GR (c-index = 0.75). For DCE-MRI, P90 ΔAUC per-pre was most predictive for pCR (c-index = 0.79). Multivariable logistic regression analyses showed complementary value when combining DW-MRI and DCE-MRI for pCR prediction (c-index = 0.89)., Conclusions: Both DW-MRI and DCE-MRI are promising in predicting response to nCRT in esophageal cancer. Combining both modalities provides complementary information, resulting in a higher predictive value.

Background: Textbook outcome is a multidimensional measure representing an ideal course after oesophagogastric cancer surgery. It comprises ten perioperative quality-of-care parameters and has been developed recently using population-based data. Its association with long-term outcome is unknown. The objectives of this study were to validate the clinical relevance of textbook outcome at a hospital level, and to assess its relation with long-term survival after treatment for oesophagogastric cancer., Methods: All patients with oesophageal or gastric cancer scheduled for surgery with curative intent between January 2009 and June 2015 were selected from an institutional database. A Cox model was used to study the association between textbook outcome and survival., Results: A textbook outcome was achieved in 58 of 144 patients (40·3 per cent) with oesophageal cancer and in 48 of 105 (45·7 per cent) with gastric cancer. Factors associated with not achieving a textbook outcome were failure to achieve a lymph node yield of at least 15 (after oesophagectomy) and postoperative complications of grade II or more. After oesophagectomy, median overall survival was longer for patients with a textbook outcome than for patients without (median not reached versus 33 months; P = 0·012). After gastrectomy, median survival was 54 versus 33 months respectively (P = 0·018). In multivariable analysis, textbook outcome was associated with overall survival after oesophagectomy (hazard ratio 2·38, 95 per cent c.i. 1·29 to 4·42) and gastrectomy (hazard ratio 2·58, 1·25 to 5·32)., Conclusion: Textbook outcome is a clinically relevant measure in patients undergoing oesophagogastric cancer surgery as it can identify underperforming parameters in a hospital setting. Overall survival in patients with a textbook outcome is better than in patients without a textbook outcome., (© 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Background: Substantial variation in the use of (neo) adjuvant treatment in patients with gastric cancer exists. The aim of this study was to identify underlying (organizational and process) factors associated with the use of perioperative therapy., Patients and Methods: Patients with resectable gastric cancer who underwent surgery between 2012 and 2014 were selected from the Dutch Upper gastrointestinal Cancer Audit (DUCA). The proportion of perioperatively treated patients was defined per hospital. Five hospitals with the lowest percentage (LP group) and 5 hospitals with the highest percentage (HP group) of perioperative therapy were identified. In the selected hospitals additional information was obtained from patients' medical records using a structured list with predefined variables., Results: In total, 429 patients (231 in LP group, 198 in HP group) from 9 different hospitals were included. Perioperative therapy was given in 16.0% of patients in the LP group compared to 40.4% in the HP group. In the LP group, patients were enrolled in a clinical trial less frequently (10.8% versus 26.8%, P<.001), and a higher percentage grade III-IV toxicity was observed during neoadjuvant treatment (25.7% versus 46.3%, P=.007). Multivariable analysis showed that, besides known casemix factors, consultation with ≥3 upper GI specialists prior to treatment decision was positively associated with initiating perioperative therapy (OR 2.08, 95% CI 1.19-3.66)., Conclusion: Results of this study confirm considerable hospital variation in the use of perioperative therapy in patients with gastric cancer. Besides known casemix factors, use of perioperative therapy was associated with the level of involvement of multidisciplinary care., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: For esophageal cancer patients treated with neoadjuvant chemoradiotherapy (nCRT), restaging using F‑18-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET-CT) following nCRT can detect interval metastases, including liver metastases, in almost 10% of patients. However, in clinical practice, focal FDG liver uptake, unrelated to liver metastases, is observed after chemoradiotherapy. This radiation-induced liver injury (RILI) can potentially lead to overstaging., Methods: A systematic search for potential cases of RILI after (chemo)radiotherapy for esophageal cancer was performed in the electronic reports from all PET-CT scans made between 2006 and 2015 in our hospital. Additional data about potential cases were obtained from the electronic medical records. A literature review of RILI was also performed., Results: Of 205 patients undergoing nCRT, 6 cases with localized increased FDG uptake in the caudate or left liver lobe following nCRT for esophageal cancer were identified. None of these patients had signs of liver metastases with additional imaging, during surgery, on biopsy, or during follow-up (range 11-46 months). At our institute, the incidence of RILI after neoadjuvant chemoradiotherapy for esophageal cancer was 3%. In the literature, RILI is described in about 8% of patients at the time of restaging. FDG-avid lesions occur in the high radiation dose area, usually corresponding to the caudate or left liver lobe., Conclusions: FDG accumulation in the caudate or left liver lobe after CRT in the area that received a high radiation dose may be caused by metastases or RILI. Awareness of the pitfall of high FDG uptake in RILI is crucial to avoid misinterpretation and overstaging.

Objective: Both the apparent diffusion coefficient (ADC) acquired by diffusion-weighted magnetic resonance imaging (DW-MRI) and the standardized uptake value (SUV), acquired by F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT), are well-established functional parameters in cancer imaging. Currently, it is unclear whether these two markers provide complementary prognostic and predictive information in esophageal cancer. The aim of this study was to evaluate the correlation between ADC and SUV in patients with esophageal cancer., Materials and Methods: This prospective study included 76 patients with histologically proven esophageal cancer who underwent both DW-MRI and F-FDG PET/CT examinations before treatment. The minimum and mean ADC values (ADCmin and ADCmean) of the primary tumor were assessed on MRI. Similarly, the glucose metabolism was evaluated by the maximum and mean SUV (SUVmax and SUVmean) in the same lesions on F-FDG PET/CT images. Spearman's rank correlation coefficients were used to assess the correlation between tumor ADC and SUV values., Results: The tumor ADC and SUV values as measures of cell density and glucose metabolism, respectively, showed negligible nonsignificant correlations (ADCmin vs. SUVmax: r=-0.087, P=0.457; ADCmin vs. SUVmean: r=-0.105, P=0.369; ADCmean vs. SUVmax: r=-0.099, P=0.349; ADCmean vs. SUVmean: r=-0.111, P=0.340). No differences in tumor ADC and SUV values were observed between the different histologic tumor types, stages, and differentiation grades., Conclusion: This study indicates that tumor cellularity derived from DW-MRI and tumor metabolism measured by F-FDG PET/CT are independent cellular phenomena in newly diagnosed esophageal cancer. Therefore, tumor ADC and SUV values may play complementary roles as imaging markers in the prediction of survival and evaluation of response to treatment in esophageal cancer.