Interim position emission tomography-computed tomography during multimodality treatment of locally advanced esophageal cancer: a scoping review

Introduction

Esophageal cancer (EC) has one of the highest incidences and mortality among cancers in Asia and other regions, with a total of 346,633 new cases and 323,600 deaths estimated to occur China in 2022, along with 19,042 new cases and 16,916 deaths estimated in the United States (1). An analysis of the CONCORD database, which comprises 290 registries across 60 countries with 730,000 patients, indicated a 5-year survival rate for patients with EC of 10–30% (2). In order to improve this low survival rate, advances in the accuracy of screening, diagnostic imaging, staging, impact of multimodality treatment, and individualized tailoring of therapies are needed.

Functional imaging performed with position emission tomography-computed tomography (PET-CT) is the gold-standard modality for patients with locally advanced disease as recognized by numerous guidelines (3,4). Fluorodeoxyglucose (FDG) PET-CT in addition to CT and endoscopic ultrasound (EUS) yields a more precise estimation of tumor volume (5). FDG PET-CT can also be used to identify the biological target volume (BTV) within the radiotherapy target volume delineation. Moreover, FDG PET-CT has been identified as a promising approach for imaging-based biomarkers in a few studies; however, there is other research that contradicts this conclusion (6).

Neoadjuvant chemoradiotherapy plus surgery has been established as the standard of care for locally advanced EC (LAEC), while neoadjuvant chemotherapy plus surgery is also popular in some regions (7). Definitive chemoradiotherapy has been globally accepted as the standard nonsurgical approach, although there are still uncertainties in the specificities of radiation dose and choice of chemotherapy regimen. Immunotherapy and targeted therapies have also added new insights to the multimodality treatment of LAEC (8).

FDG PET-CT can be used to predict outcome and prognosis in the pretreatment setting and has been used increasingly in assessing treatment response (9). FDG PET-CT provides various prognostic metabolic parameters, including the standardized uptake value (SUV), which is semiquantitatively assessed by glucose uptake; metabolic tumor volume (MTV), which is defined as the volume of tumor tissue with increased FDG uptake; and tumor lesion glycolysis (TLG), which is the product of MTV multiplied by the SUV (10). The SUV is a widely used semiquantitative metric for assessing tissue accumulation of tracers, and it can be normalized to body mass, lean body mass (SUL), or body surface area. The change in SUVmax is the most frequently used parameter for evaluating tumor metabolic change during treatment and obtaining prognostic information.

There has been increasing interest in the prognostic and predictive benefit of FDG PET-CT acquired at a time point during bimodality (chemoradiation) or trimodality (chemoradiaiton followed by surgery) treatment, defined as interim FDG PET (PETint) (11). Early identification of progressive disease may expedite resection or may alternatively lead to the abandonment of a curative surgical approach; additionally, systemic therapy and/or radiation schedules can be modified (12). A scoping review was conducted to evaluate the current evidence in neoadjuvant chemoradiotherapy, definitive chemoradiotherapy, and adaptive radiotherapy concerning the value of FDG PETint in the bimodality or trimodality management of LAEC, with a focus on its prognostic and predictive capability. We present this article in accordance with the PRISMA-ScR reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1306/rc).

Methods

A systematic scoping search of the MEDLINE database from January 1, 2001, to January 1, 2022, was conducted with the following search terms: (esophageal carcinoma OR esophageal cancer OR oesophageal carcinoma OR oesophageal cancer) AND (chemoradiotherapy or chemoradiation or therapy) AND (FDG OR 18F FDG) AND (PET OR PET-CT) AND (predictive OR prediction OR response assessment OR response OR assessment). A medical subject heading (MeSH) search was also performed as follows: (esophageal neoplasms [MeSH]) AND (positron emission tomography [MeSH]) AND (18F FDG [MeSH]) AND (chemoradiotherapy [MeSH]) AND predictive value of tests [MeSH]). In addition, the references of selected articles were manually checked to identify other articles meeting the inclusion criteria. The search date was January 1, 2022.

Screening was conducted by 2 independent assessors (HZ and SH). Literature was selected for full-text review if the abstract reported on tumor response assessment after neoadjuvant chemo(radio) therapy or definitive chemoradiotherapy in EC. The full English text of relevant studies was retrieved for further selection. A flow diagram of the literature screening is shown in Figure 1. Only original articles were included. The full exclusion criteria were as follows: reviews, guidelines, letters, editorials, case reports; publications not in English; use of a PET only (rather than PET-CT); radiopharmaceuticals other than FDG; publications based on diagnosis, staging, or restaging for recurrent cancer; and nonhuman studies. The following information was extracted: author, year, region, nature of study, number of patients, treatment regimen, PET timing, metabolic parameters and cutoff, and correlation of PET with clinical response, survival, and histopathology (for neoadjuvant studies).

Figure 1 Flow diagram for literature screening. PET-CT, position emission tomography-computed tomography.

Results

After screening, 63 articles were included in this review: 27 prospective and 36 retrospective studies. Table 1 summarizes the 57 articles focusing on detecting residual disease during or after completion of neoadjuvant treatment prior to surgery in trimodality management, including 18 from the United States (15,17,20,23,24,27,28,31,32,35,39,43,45,49,52,54,57,63), 6 from Germany (13,19,26,30,33,38), 6 from Korea (21,25,44,51,53,64), 5 from Japan (16,59,60,61,62), 4 from Ireland (22,34,47,56), 4 from The Netherlands (37,48,55,68), 3 from France (41,42,67), 3 from China (40,50,66), 1 from Belgium (14), 1 from Australia (29), 1 from Czechia (36), 1 from Canada (46), 1 from India (58), 1 from Pakistan (65), and 1 from Spain (69). Table 2 summarizes the 5 articles the focused on identifying poor responders or nonresponders during definitive chemoradiation (70-74), 2 of which describe the same study (71,72). One single study describes adaptive radiotherapy based on the use of molecular PET imaging (75).

Neoadjuvant chemoradiotherapy

A total of 57 studies involving 4,823 patients assessed response to neoadjuvant chemoradiotherapy during or after planned trimodality treatment (Table 1). Of these, 27 reported a favorable value of FDG PET-CT in predicting pathological response. Treatment details of the studies were as follows: the radiation doses ranged from 25–59.4 Gy, with almost half of the studies (28/59) using 41.4–50.4 Gy; and chemotherapy regimens were predominantly based on cisplatin (DDP), 5-fluorouracil (5-FU), or paclitaxel (PTX), with 56% using doublet DDP/5-FU. Moreover, 48 studies evaluated quantitative PET for the primary tumor by using SUVmax, while 30 studies reported a percentage reduction of SUVmax (%SUVmax), with the median cutoff values varying from 10% to 70%, and more than one-third (11/30) of these reporting values of 50–60%. SUVmean was reported in 7 studies, and 10 studies focused on qualitative synthesis (MTV, TLG), evaluating metabolic complete response (mCR) for residual disease at the primary tumor. Finally, 2 studies investigated and validated a clinical parameter model for predicting pathologic response following EC neoadjuvant chemoradiation (38,59).

Definitive chemoradiotherapy

There were 4 studies comprising 312 patients, all describing definitive chemoradiotherapy for squamous cell carcinoma, 1 of which was prospective (70-74) and 3 of which were conducted in Asia. In this approach, radiation doses ranged from 50–66 Gy, with concurrent chemotherapy regimens being similar to the trimodality schedules described above. The timing of PETint after the start of CRT ranged from 21 days to 5 weeks. One study included 4 serial PETs (prior to radiation therapy at 50 Gy, on completion of radiation, and 1 month after) (73). PET parameters included qualitative, semiquantitative (SUVmax, SUVmean, SUVmax, ΔSUVmean), and quantitative (MTV, TLG) measures. Two of the studies reported a favorable role of PETint in predicting local control, and the other two reported favorably on its ability to predict survival. The Chinese study by Yang et al. suggested that a 51% decrease in FDG uptake during chemoradiation was a sensitive and accurate cutoff point for predicting progression-free survival (PFS) (70). Li et al. analyzed 160 patients with esophageal squamous cell carcinoma (ESCC) and concluded that sequential FDG PET-CT scanning is useful for predicting the overall survival of patients treated with chemoradiotherapy for ESCC (73). The prospective French study of 57 patients indicated that a larger tumor volume and higher SUVmax/TLG were associated with poor outcome at 3 months, with a higher SUVmax values also predicting a poor outcome at 1 year (71,72). Chen et al. used fluorothymidine (FLT) and showed that early interim 3'-Deoxy-3'-[18F]-FLT PET-CT was a significant predictor of 2-year PFS and locoregional recurrence (LR) and was more correlated with early responses and late outcomes than was interim FDG PET-CT (74).

Adaptive radiotherapy

One prospective study of 10 patients reported the role of PET for adaptive radiotherapy, which incorporates changes in anatomy and/or deviations in planned delivered dose due to deviations in patient setup or variability machine delivery to estimate the actual delivered dose to a patient as the treatment progresses (76). The authors compared treatment plan simulations with combinations of 50 or 66 Gy, with the volumes defined in FDG PET-CT images prior and during radiotherapy. When the total dose was increased to the target volume, planning based on the MTV of the initial FDG PET-CT resulted in significantly lower doses to the organs at risk (OARs), including the spinal cord and the lungs.

Discussion

The role of interim PET-CT during multimodality treatment of LAEC has considerable importance, and yet, to date, most of the related studies have been small and retrospective in design. While some studies reported positive results of PETint in predicting local control or survival, there are many studies that did not reach this conclusion. Differences in PET parameters, which themselves are hard to standardize given the radiopharmaceutical nature of the test, variation in time points, and intrinsic prognostic factors, such as tumor histology and patient ethnicity, contribute to the heterogeneity of the studies and impact the interpretation of results. Other specific issues are discussed below.

Identification of microscopic residual disease

Across all cancers, the challenge of detecting microscopic disease, in this case residual foci during or following intensive treatment, remains a challenge that has yet to be overcome. Predicting complete pathological response (pCR) potentially alleviates need for inclusion of surgery, which would be a major advance for patients in terms of morbidity, mortality, and quality of life (75,77). This “organ preservation” approach is more advanced in other gastrointestinal cancers, particularly rectal cancer, and typically uses a combination of clinical and diagnostic imaging to determine to confirm a lack microscopic residual cancer. The smallest amount of residual disease should ideally be detected, although the recent demonstration of the efficacy of adjuvant therapy with checkpoint inhibitors may ultimately also facilitate this. A more nuanced understanding concerning which patients benefit from immunotherapy is anticipated. The role of PETint in combination with other assessments including serial biopsies and circulating tumor DNA (ctDNA) is a field with considerable potential (78-80).

Qualitative versus quantitative PET-CT evaluation

Different methods have been proposed to evaluate the FDG PET-CT images in EC, including visual assessment (qualitative) and semiquantitative (SUV) and quantitative analyses (81). However, the best method for balancing the accuracy, practicality, and clinical applicability in PET has not been established. PET Response Criteria in Solid Tumors (PERCIST) has been used in practice and clinical trials in EC and some other types of solid tumors (82). The standardization of acquisition and reconstruction data remain key limitations, while patient preparation and the calibration of the PET-CT scanner are also relevant. The intrinsic basal variability of SUVmax may also hamper the early treatment response prediction in patients with EC. No ΔSUVmax cutoff value has been established for defining subgroups of prognoses, and there is a need to standardize this for clinical trials as well as routine practice. Future studies are warranted to determine the ΔSUVmax cutoff values that are useful for the early identification of patients with poor treatment outcomes.

Timing

The optimal timing for FDG PET-CTint has yet to be determined for EC. For esophageal patients with favorable early treatment response, a deintensification of the therapy to maximize the therapeutic ratio may be beneficial (83). Meanwhile, for EC, patients showing no response to treatment could benefit from a timely modification of the treatment strategy or an intensification of treatment. It is often not appreciated that radiation-induced inflammation of the peritumoral mucosal tissues can affect the interpretation of images in both the early and late phases of chemoradiation (12). The likelihood of obtaining false-positive results may increase due to radiation-induced inflammation as the radiation dose increases. A 2-week interval is one reported timing of FDG-PETint, while the consistency of a 2-week interval for the evaluation of treatment response is not supported by the literature. In this time frame, the actual delivered radiation dose may be around 20–30 Gy. However, PETint at a radiation dose >30 Gy may be more suitable for producing a decrease in FDG uptake that can be correlated with clinical outcome (83). Waiting a total of 8–16 weeks after completion of chemoradiation may be useful for assessing treatment response and providing prognostic information in EC, but in trimodality schedules, surgery is usually performed well before this (84). Designing a study to optimize the timing of PETint would be challenging but highly valued.

Biologically adaptive radiotherapy

The implementation of adaptive radiotherapy schemes presents several challenges, including devising an adequate delineation method and a means for deformable image registration, etc. Adaptive radiotherapy can generally mean 3 meanings: (I) treatment plan modification during a course of radiotherapy to account for temporal changes in anatomy, such as, internal motion, tumor shrinkage, and weight loss); (II) adjustment of radiation dose delivery based on early tumor response, such as boosting the residual imaged tumor; and (III) treatment strategy adaptation based on early tumor response, such as shifting chemotherapy regimens and adding systematic therapies or sensitizers. Molecular imaging integrated into the anatomic information is one of the most promising approaches in adaptive radiotherapy. In this method, radiosensitivity differences within the tumor can be identified, and a heterogeneous dose distribution can be achieved to allow for better local control.

Limitations

There are some limitations to this review that should be noted. First, the studies reviewed often reported conflicting findings, and thus a definitive conclusion cannot be drawn. Second, the heterogeneity of the studies may be confusing and inconclusive. Third, evidence concerning many issues of PETint, such as the time and parameters, was lacking. More well-designed clinical studies are warranted to investigate the more important clinical questions. Fourth, the current review focused on studies from the past 20 years (January 2001 to January 2022), and recent findings that could provide novel insights might have been missed.

Conclusions

This scoping review found PETint to have prognostic value in a variety of situations. However, there is a need to improve its accuracy, which will likely be achieved through a greater standardization of measurements and reporting within the testing, in addition to combination with other promising measures of response and residual disease.

Acknowledgments

Funding: This work was supported by the National Natural Science Foundation of China (No. 82102827), Chinese Society of Clinical Oncology (No. Y-Young2020-0003), and the Beijing Bethune Charitable Foundation (No. flzh202119).

Footnote

Reporting Checklist: The authors have completed the PRISMA-ScR reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-22-1306/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-1306/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N, Chen W. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl) 2022;135:584-90. [Crossref] [PubMed]
2. Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Nikšić M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018;391:1023-75. [Crossref] [PubMed]
3. Ajani JA, D’Amico TA, Bentrem DJ, Chao J, Corvera C, Das P, et al. Esophageal and Esophagogastric Junction Cancers, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019;17:855-83. [Crossref] [PubMed]
4. Muro K, Lordick F, Tsushima T, Pentheroudakis G, Baba E, Lu Z, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS. Ann Oncol 2019;30:34-43. [Crossref] [PubMed]
5. Eyck BM, Onstenk BD, Noordman BJ, Nieboer D, Spaander MCW, Valkema R, Lagarde SM, Wijnhoven BPL, van Lanschot JJB. Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Systematic Review and Meta-analysis. Ann Surg 2020;271:245-56. [Crossref] [PubMed]
6. Lordick F, Ott K, Krause BJ. New trends for staging and therapy for localized gastroesophageal cancer: the role of PET. Ann Oncol 2010;21:vii294-9. [Crossref] [PubMed]
7. Li B, Zhang Y, Miao L, Ma L, Luo X, Zhang Y, et al. Esophagectomy With Three-Field Versus Two-Field Lymphadenectomy for Middle and Lower Thoracic Esophageal Cancer: Long-Term Outcomes of a Randomized Clinical Trial. J Thorac Oncol 2021;16:310-7. [Crossref] [PubMed]
8. Li Y, Liu J, Cai XW, Li HX, Cheng Y, Dong XH, Yu W, Fu XL. Biomarkers for the prediction of esophageal cancer neoadjuvant chemoradiotherapy response: A systemic review. Crit Rev Oncol Hematol 2021;167:103466. [Crossref] [PubMed]
9. Wu AJ, Goodman KA. Positron emission tomography imaging for gastroesophageal junction tumors. Semin Radiat Oncol 2013;23:10-5. [Crossref] [PubMed]
10. de Gouw DJJM, Klarenbeek BR, Driessen M, Bouwense SAW, van Workum F, Fütterer JJ, Rovers MM, Ten Broek RPG, Rosman C. Detecting Pathological Complete Response in Esophageal Cancer after Neoadjuvant Therapy Based on Imaging Techniques: A Diagnostic Systematic Review and Meta-Analysis. J Thorac Oncol 2019;14:1156-71. [Crossref] [PubMed]
11. Zhu W, Xing L, Yue J, Sun X, Sun X, Zhao H, Yu J. Prognostic significance of SUV on PET/CT in patients with andomize oesophagogastric junction cancer receiving neoadjuvant chemotherapy/chemoradiation:a systematic review and meta-analysis. Br J Radiol 2012;85:e694-701. [Crossref] [PubMed]
12. Lu J, Sun XD, Yang X, Tang XY, Qin Q, Zhu HC, Cheng HY, Sun XC. Impact of PET/CT on radiation treatment in patients with esophageal cancer: A systematic review. Crit Rev Oncol Hematol 2016;107:128-37. [Crossref] [PubMed]
13. Brücher BL, Weber W, Bauer M, Fink U, Avril N, Stein HJ, Werner M, Zimmerman F, Siewert JR, Schwaiger M. Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography. Ann Surg 2001;233:300-9. [Crossref] [PubMed]
14. Flamen P, Van Cutsem E, Lerut A, Cambier JP, Haustermans K, Bormans G, De Leyn P, Van Raemdonck D, De Wever W, Ectors N, Maes A, Mortelmans L. Positron emission tomography for assessment of the response to induction radiochemotherapy in locally advanced oesophageal cancer. Ann Oncol 2002;13:361-8. [Crossref] [PubMed]
15. Arslan N, Miller TR, Dehdashti F, Battafarano RJ, Siegel BA. Evaluation of response to neoadjuvant therapy by quantitative 2-deoxy-2-[18F]fluoro-D-glucose with positron emission tomography in patients with esophageal cancer. Mol Imaging Biol 2002;4:301-10.
16. Kato H, Kuwano H, Nakajima M, Miyazaki T, Yoshikawa M, Masuda N, Fukuchi M, Manda R, Tsukada K, Oriuchi N, Endo K. Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer. Am J Surg 2002;184:279-83. [Crossref] [PubMed]
17. Downey RJ, Akhurst T, Ilson D, Ginsberg R, Bains MS, Gonen M, Koong H, Gollub M, Minsky BD, Zakowski M, Turnbull A, Larson SM, Rusch V. Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial. J Clin Oncol 2003;21:428-32. [Crossref] [PubMed]
18. Wieder HA, Brücher BL, Zimmermann F, Becker K, Lordick F, Beer A, Schwaiger M, Fink U, Siewert JR, Stein HJ, Weber WA. Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment. J Clin Oncol 2004;22:900-8. [Crossref] [PubMed]
19. Brink I, Hentschel M, Bley TA, Walch A, Mix M, Kleimaier M, Moser E, Imdahl A. Effects of neoadjuvant radio-chemotherapy on 18F-FDG-PET in esophageal carcinoma. Eur J Surg Oncol 2004;30:544-50. [Crossref] [PubMed]
20. Swisher SG, Maish M, Erasmus JJ, Correa AM, Ajani JA, Bresalier R, Komaki R, Macapinlac H, Munden RF, Putnam JB, Rice D, Smythe WR, Vaporciyan AA, Walsh GL, Wu TT, Roth JA. Utility of PET, CT, and EUS to identify pathologic responders in esophageal cancer. Ann Thorac Surg 2004;78:1152-60; discussion 1152-60. [Crossref] [PubMed]
21. Song SY, Kim JH, Ryu JS, Lee GH, Kim SB, Park SI, Song HY, Cho KJ, Ahn SD, Lee SW, Shin SS, Choi EK. FDG-PET in the prediction of pathologic response after neoadjuvant chemoradiotherapy in locally advanced, resectable esophageal cancer. Int J Radiat Oncol Biol Phys 2005;63:1053-9. [Crossref] [PubMed]
22. Gillham CM, Lucey JA, Keogan M, Duffy GJ, Malik V, Raouf AA, O’byrne K, Hollywood D, Muldoon C, Reynolds JV. (18)FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response. Br J Cancer 2006;95:1174-9. [Crossref] [PubMed]
23. Levine EA, Farmer MR, Clark P, Mishra G, Ho C, Geisinger KR, Melin SA, Lovato J, Oaks T, Blackstock AW. Predictive value of 18-fluoro-deoxy-glucose-positron emission tomography (18F-FDG-PET) in the identification of responders to chemoradiation therapy for the treatment of locally advanced esophageal cancer. Ann Surg 2006;243:472-8. [Crossref] [PubMed]
24. Bruzzi JF, Swisher SG, Truong MT, Munden RF, Hofstetter WL, Macapinlac HA, Correa AM, Mawlawi O, Ajani JA, Komaki RR, Fukami N, Erasmus JJ. Detection of interval distant metastases: clinical utility of integrated CT-PET imaging in patients with esophageal carcinoma after neoadjuvant therapy. Cancer 2007;109:125-34. [Crossref] [PubMed]
25. Kim MK, Ryu JS, Kim SB, Ahn JH, Kim SY, Park SI, Kim YH, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Value of complete metabolic response by (18)F-fluorodeoxyglucose-positron emission tomography in oesophageal cancer for prediction of pathologic response and survival after preoperative chemoradiotherapy. Eur J Cancer 2007;43:1385-91. [Crossref] [PubMed]
26. Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, Lorenzen S, Schuster T, Wieder H, Herrmann K, Bredenkamp R, Höfler H, Fink U, Peschel C, Schwaiger M, Siewert JR. PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol 2007;8:797-805. [Crossref] [PubMed]
27. Mamede M. Abreu-E-Lima P, Oliva MR, Nosé V, Mamon H, Gerbaudo VH. FDG-PET/CT tumor segmentation-derived indices of metabolic activity to assess response to neoadjuvant therapy and progression-free survival in esophageal cancer: correlation with histopathology results. Am J Clin Oncol 2007;30:377-88. [Crossref] [PubMed]
28. McLoughlin JM, Melis M, Siegel EM, Dean EM, Weber JM, Chern J, Elliott M, Kelley ST, Karl RC. Are patients with esophageal cancer who become PET negative after neoadjuvant chemoradiation free of cancer? J Am Coll Surg 2008;206:879-86; discussion 886-7. [Crossref] [PubMed]
29. Smithers BM, Couper GC, Thomas JM, Wong D, Gotley DC, Martin I, Harvey JA, Thomson DB, Walpole ET, Watts N, Burmeister BH. Positron emission tomography and pathological evidence of response to neoadjuvant therapy in adenocarcinoma of the esophagus. Dis Esophagus 2008;21:151-8. [Crossref] [PubMed]
30. Vallböhmer D, Hölscher AH, Dietlein M, Bollschweiler E, Baldus SE, Mönig SP, Metzger R, Schicha H, Schmidt M. [18F]-Fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg 2009;250:888-94. [Crossref] [PubMed]
31. Javeri H, Xiao L, Rohren E, Lee JH, Liao Z, Hofstetter W, Maru D, Bhutani MS, Swisher SG, Macapinlac H, Wang X, Ajani JA. The higher the decrease in the standardized uptake value of positron emission tomography after chemoradiation, the better the survival of patients with gastroesophageal adenocarcinoma. Cancer 2009;115:5184-92. [Crossref] [PubMed]
32. Roedl JB, Colen RR, Holalkere NS, Fischman AJ, Choi NC, Blake MA. Adenocarcinomas of the esophagus: response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation. Radiother Oncol 2008;89:278-86. [Crossref] [PubMed]
33. Schmidt M, Bollschweiler E, Dietlein M, Mönig SP, Kobe C, Vallböhmer D, Eschner W, Hölscher A, Schicha H. Mean and maximum standardized uptake values in 18FFDG-PET for assessment of histopathological response in oesophageal squamous cell carcinoma or adenocarcinoma after radiochemotherapy. Eur J Nucl Med Mol Imaging 2009;36:735-44. [Crossref] [PubMed]
34. Malik V, Lucey JA, Duffy GJ, Wilson L, McNamara L, Keogan M, Gillham C, Reynolds JV. Early repeated 18F-FDG PET scans during neoadjuvant chemoradiation fail to predict histopathologic response or survival benefit in adenocarcinoma of the esophagus. J Nucl Med 2010;51:1863-9. [Crossref] [PubMed]
35. Monjazeb AM, Riedlinger G, Aklilu M, Geisinger KR, Mishra G, Isom S, Clark P, Levine EA, Blackstock AW. Outcomes of patients with esophageal cancer staged with [¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection? J Clin Oncol 2010;28:4714-21.
36. Myslivecek M, Neoral C, Vrba R, Vomackova K, Cincibuch J, Formanek R, Koranda P, Zapletalova J. The value of ¹⁸F-FDG PET/CT in assessment of metabolic response in esophageal cancer for prediction of histopathological response and survival after preoperative chemoradiotherapy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012;156:171-9. [Crossref] [PubMed]
37. van Heijl M, Omloo JM, van Berge Henegouwen MI, Hoekstra OS, Boellaard R, Bossuyt PM, Busch OR, Tilanus HW, Hulshof MC, van der Gaast A, Nieuwenhuijzen GA, Bonenkamp HJ, Plukker JT, Cuesta MA, Ten Kate FJ, Pruim J, van Dekken H, Bergman JJ, Sloof GW, van Lanschot JJ. Fluorodeoxyglucose positron emission tomography for evaluating early response during neoadjuvant chemoradiotherapy in patients with potentially curable esophageal cancer. Ann Surg 2011;253:56-63.
38. zum Büschenfelde CM, Herrmann K, Schuster T, Geinitz H, Langer R, Becker K, Ott K, Ebert M, Zimmermann F, Friess H, Schwaiger M, Peschel C, Lordick F, Krause BJ. (18)F-FDG PET-guided salvage neoadjuvant radiochemotherapy of adenocarcinoma of the esophagogastric junction: the MUNICON II trial. J Nucl Med 2011;52:1189-96. [Crossref] [PubMed]
39. Jayachandran P, Pai RK, Quon A, Graves E, Krakow TE, La T, Loo BW Jr, Koong AC, Chang DT. Postchemoradiotherapy positron emission tomography predicts pathologic response and survival in patients with esophageal cancer. Int J Radiat Oncol Biol Phys 2012;84:471-7. [Crossref] [PubMed]
40. Yen TJ, Chung CS, Wu YW, Yen RF, Cheng MF, Lee JM, Hsu CH, Chang YL, Wang HP. Comparative study between endoscopic ultrasonography and positron emission tomography-computed tomography in staging patients with esophageal squamous cell carcinoma. Dis Esophagus 2012;25:40-7. [Crossref] [PubMed]
41. Piessen G, Petyt G, Duhamel A, Mirabel X, Huglo D, Mariette C. Ineffectiveness of ¹⁸F-fluorodeoxyglucose positron emission tomography in the evaluation of tumor response after completion of neoadjuvant chemoradiation in esophageal cancer. Ann Surg 2013;258:66-76. [Crossref] [PubMed]
42. Cuenca X, Hennequin C, Hindié E, Rivera S, Vercellino L, Baruch-Hennequin V, Gornet JM, Cattan P, Chirica M, Quéro L. Evaluation of early response to concomitant chemoradiotherapy by interim 18F-FDG PET/CT imaging in patients with locally advanced oesophageal carcinomas. Eur J Nucl Med Mol Imaging 2013;40:477-85. [Crossref] [PubMed]
43. Cheedella NK, Suzuki A, Xiao L, Hofstetter WL, Maru DM, Taketa T, Sudo K, Blum MA, Lin SH, Welch J, Lee JH, Bhutani MS, Rice DC, Vaporciyan AA, Swisher SG, Ajani JA. Association between clinical complete response and pathological complete response after preoperative chemoradiation in patients with gastroesophageal cancer: analysis in a large cohort. Ann Oncol 2013;24:1262-6. [Crossref] [PubMed]
44. Park JS, Choi JY, Moon SH, Ahn YC, Lee J, Kim D, Kim K, Shim YM. Response evaluation after neoadjuvant chemoradiation by positron emission tomography-computed tomography for esophageal squamous cell carcinoma. Cancer Res Treat 2013;45:22-30. [Crossref] [PubMed]
45. Stiles BM, Salzler G, Jorgensen A, Nasar A, Paul S, Lee PC, Port JL, Altorki NK. Complete metabolic response is not uniformly predictive of complete pathologic response after induction therapy for esophageal cancer. Ann Thorac Surg 2013;96:1820-5. [Crossref] [PubMed]
46. Metser U, Rashidi F, Moshonov H, Wong R, Knox J, Guindi M, Darling G. (18)F-FDG-PET/CT in assessing response to neoadjuvant chemoradiotherapy for potentially resectable locally advanced esophageal cancer. Ann Nucl Med 2014;28:295-303. [Crossref] [PubMed]
47. Elliott JA, O’Farrell NJ, King S, Halpenny D, Malik V, Muldoon C, Johnston C, Reynolds JV. Value of CT-PET after neoadjuvant chemoradiation in the prediction of histological tumour regression, nodal status and survival in oesophageal adenocarcinoma. Br J Surg 2014;101:1702-11. [Crossref] [PubMed]
48. Stiekema J, Vermeulen D, Vegt E, Voncken FE, Aleman BM, Sanders J, Boot H, van Sandick JW. Detecting interval metastases and response assessment using 18F-FDG PET/CT after neoadjuvant chemoradiotherapy for esophageal cancer. Clin Nucl Med 2014;39:862-7. [Crossref] [PubMed]
49. Elimova E, Wang X, Etchebehere E, Shiozaki H, Shimodaira Y, Wadhwa R, Planjery V, Charalampakis N, Blum MA, Hofstetter W, Lee JH, Weston BR, Bhutani MS, Rogers JE, Maru D, Skinner HD, Macapinlac HA, Ajani JA. 18-fluorodeoxy-glucose positron emission computed tomography as predictive of response after chemoradiation in oesophageal cancer patients. Eur J Cancer 2015;51:2545-52. [Crossref] [PubMed]
50. Yuan H, Tong DK, Vardhanabhuti V, Law SY, Chiu KW, Khong PL. PET/CT in the evaluation of treatment response to neoadjuvant chemoradiotherapy and prognostication in patients with locally advanced esophageal squamous cell carcinoma. Nucl Med Commun 2016;37:947-55. [Crossref] [PubMed]
51. Kim JJ, Park JK, Moon SW. Usefulness of positron emission tomography-computed tomography in pre-operative evaluation of intra-thoracic esophageal cancer. Thorac Cancer 2015;6:687-94. [Crossref] [PubMed]
52. Kukar M, Alnaji RM, Jabi F, Platz TA, Attwood K, Nava H, Ben-David K, Mattson D, Salerno K, Malhotra U, Kanehira K, Gannon J, Hochwald SN. Role of Repeat 18F-Fluorodeoxyglucose Positron Emission Tomography Examination in Predicting Pathologic Response Following Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma. JAMA Surg 2015;150:555-62. [Crossref] [PubMed]
53. Kim SJ, Koo PJ, Chang S. Predictive value of repeated F-18 FDG PET/CT parameters changes during preoperative chemoradiotherapy to predict pathologic response and overall survival in locally advanced esophageal adenocarcinoma patients. Cancer Chemother Pharmacol 2016;77:723-31. [Crossref] [PubMed]
54. Chang S, Koo PJ, Kwak JJ, Kim SJ. Changes in Total Lesion Glycolysis Evaluated by Repeated F-18 FDG PET/CT as Prognostic Factor in Locally Advanced Esophageal Cancer Patients Treated with Preoperative Chemoradiotherapy. Oncology 2016;90:97-102. [Crossref] [PubMed]
55. Hagen PV, Heijl MV, Henegouwen MI, Boellaard R, Bossuyt PM, Kate FJ, Dekken HV, Hoekstra OS, Sloof GW, Lanschot JJ. Prediction of disease-free survival using relative change in FDG-uptake early during neoadjuvant chemoradiotherapy for potentially curable esophageal cancer: A prospective cohort study. Dis Esophagus 2017;30:1-7. [Crossref] [PubMed]
56. Heneghan HM, Donohoe C, Elliot J, Ahmed Z, Malik V, Ravi N, Reynolds JV. Can CT-PET and Endoscopic Assessment Post-Neoadjuvant Chemoradiotherapy Predict Residual Disease in Esophageal Cancer? Ann Surg 2016;264:831-8. [Crossref] [PubMed]
57. Arnett ALH, Merrell KW, Macintosh EM, James SE, Nathan MA, Shen KR, Ravi K, Neben Wittich MA, Haddock MG, Hallemeier CL. Utility of (18)F-FDG PET for Predicting Histopathologic Response in Esophageal Carcinoma following Chemoradiation. J Thorac Oncol 2017;12:121-8. [Crossref] [PubMed]
58. Dewan A, Sharma SK, Dewan AK, Khurana R, Gupta M, Pahuja A, Srivastava H, Sinha R. Impact on Radiological and Pathological Response with Neoadjuvant Chemoradiation and Its Effect on Survival in Squamous Cell Carcinoma of Thoracic Esophagus. J Gastrointest Cancer 2017;48:42-9. [Crossref] [PubMed]
59. Hamai Y, Hihara J, Emi M, Furukawa T, Yamakita I, Kurokawa T, Okada M. Ability of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography to Predict Outcomes of Neoadjuvant Chemoradiotherapy Followed by Surgical Treatment for Esophageal Squamous Cell Carcinoma. Ann Thorac Surg 2016;102:1132-9. [Crossref] [PubMed]
60. Makino T, Yamasaki M, Tanaka K, Tatsumi M, Takiguchi S, Hatazawa J, Mori M, Doki Y. Importance of positron emission tomography for assessing the response of primary and metastatic lesions to induction treatments in T4 esophageal cancer. Surgery 2017;162:836-45. [Crossref] [PubMed]
61. Sasaki K, Uchikado Y, Okumura H, Omoto I, Kita Y, Arigami T, Uenosono Y, Owaki T, Maemura K, Natsugoe S. Role of (18)F-FDG-PET/CT in Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemoradiotherapy. Anticancer Res 2017;37:859-64. [Crossref] [PubMed]
62. Motoyama S, Sato Y, Sasaki T, Wakita A, Kawakita Y, Liu J, Nagaki Y, Saito H, Imai K, Konno H, Mizusawa KT, Minamiya Y. Efficacy and Safety of Neoadjuvant Chemoradiotherapy Following Esophagectomy with Japanese-style Extended 3-Field Lymphadenectomy for Thoracic Esophageal Cancer. Anticancer Res 2017;37:5837-43. [Crossref] [PubMed]
63. Tandberg DJ, Cui Y, Rushing CN, Hong JC, Ackerson BG, Marin D, Zhang X, Czito BG, Willett CW, Palta M. Intratreatment Response Assessment With 18F-FDG PET: Correlation of Semiquantitative PET Features With Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiotherapy. Int J Radiat Oncol Biol Phys 2018;102:1002-7. [Crossref] [PubMed]
64. Kim N, Cho H, Yun M, Park KR, Lee CG. Prognostic values of mid-radiotherapy (18)F-FDG PET/CT in patients with esophageal cancer. Radiat Oncol 2019;14:27. [Crossref] [PubMed]
65. Fatima N, Zaman MU, Zaman A, Zaman U, Tahseen R, Zaman S. Staging and Response Evaluation to Neo-Adjuvant Chemoradiation in Esophageal Cancers Using 18FDG PET/ CT with Standardized Protocol. Asian Pac J Cancer Prev 2019;20:2003-8. [Crossref] [PubMed]
66. Huang YC, Lu HI, Huang SC, Hsu CC, Chiu NT, Wang YM, Chiu YC, Li SH. FDG PET using SUV(max) for preoperative T-staging of esophageal squamous cell carcinoma with and without neoadjuvant chemoradiotherapy. BMC Med Imaging 2017;17:1. [Crossref] [PubMed]
67. Hammoudi N, Hennequin C, Vercellino L, Costantini A, Valverde A, Cattan P, Quéro L. Early metabolic response to chemoradiotherapy by interim FDG PET/CT is associated with better overall survival and histological response in esophageal cancers. Dig Liver Dis 2019;51:887-93. [Crossref] [PubMed]
68. Valkema MJ, Noordman BJ, Wijnhoven BPL, Spaander MCW, Biermann K, Lagarde SM, Bennink RJ, Schreurs WMJ, Roef MJ, Hobbelink MGG, Janssen MJR, Graven LH, van Lanschot JJB, Valkema R. Accuracy of (18)F-FDG PET/CT in Predicting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer. J Nucl Med 2019;60:1553-9. [Crossref] [PubMed]
69. Sánchez-Izquierdo N, Perlaza P, Pagès M, Buxó E, Rios J, Rubello D, Colletti PM, Mayoral M, Casanueva S, Fernández-Esparrach G, Ginés A, Fuster D. Assessment of Response to Neoadjuvant Chemoradiotherapy by 18F-FDG PET/CT in Patients With Locally Advanced Esophagogastric Junction Adenocarcinoma. Clin Nucl Med 2020;45:38-43. [Crossref] [PubMed]
70. Yang Y, Yang Z, Han A, Feng R, Ma Y, Kong L, Sun X, Zheng J, Yu J. Prediction of the outcome of definitive chemoradiation by decrease in F-18 FDG uptake in nonsurgical esophageal squamous cell cancer. Clin Nucl Med 2011;36:860-6. [Crossref] [PubMed]
71. Palie O, Michel P, Ménard JF, Rousseau C, Rio E, Bridji B, Benyoucef A, Meyer ME, Jalali K, Bardet S, M’vondo CM, Olivier P, Faure G, Itti E, Diana C, Houzard C, Mornex F, Di Fiore F, Vera P. The predictive value of treatment response using FDG PET performed on day 21 of chemoradiotherapy in patients with oesophageal squamous cell carcinoma. A prospective, multicentre study (RTEP3). Eur J Nucl Med Mol Imaging 2013;40:1345-55. [Crossref] [PubMed]
72. Vera P, Dubray B, Palie O, Buvat I, Hapdey S, Modzelewski R, Benyoucef A, Rousseau C, Meyer ME, Bardet S, Gardin I, Fiore FD, Michel P. Monitoring tumour response during chemo-radiotherapy: a parametric method using FDG-PET/CT images in patients with oesophageal cancer. EJNMMI Res 2014;4:12. [Crossref] [PubMed]
73. Li Y, Lin Q, Luo Z, Zhao L, Zhu L, Sun L, Wu H. Value of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in prediction of the overall survival of esophageal cancer patients treated with chemoradiotherapy. Int J Clin Exp Med 2015;8:10947-55.
74. Chen H, Li Y, Wu H, Sun L, Lin Q, Zhao L, An H. 3’-deoxy-3’-[¹⁸F]-fluorothymidine PET/CT in early determination of prognosis in patients with esophageal squamous cell cancer: comparison with [¹⁸F]-FDG PET/CT. Strahlenther Onkol 2015;191:141-52.
75. Borggreve AS, Goense L, van Rossum PSN, Heethuis SE, van Hillegersberg R, Lagendijk JJW, Lam MGEH, van Lier ALHMW, Mook S, Ruurda JP, van Vulpen M, Voncken FEM, Aleman BMP, Bartels-Rutten A, Ma J, Fang P, Musall BC, Lin SH, Meijer GJ. Preoperative Prediction of Pathologic Response to Neoadjuvant Chemoradiotherapy in Patients With Esophageal Cancer Using (18)F-FDG PET/CT and DW-MRI: A Prospective Multicenter Study. Int J Radiat Oncol Biol Phys 2020;106:998-1009. [Crossref] [PubMed]
76. Nkhali L, Thureau S, Edet-Sanson A, Doyeux K, Benyoucef A, Gardin I, Michel P, Vera P, Dubray B. FDG-PET/CT during concomitant chemo radiotherapy for esophageal cancer: Reducing target volumes to deliver higher radiotherapy doses. Acta Oncol 2015;54:909-15. [Crossref] [PubMed]
77. Borggreve AS, Mook S, Verheij M, Mul VEM, Bergman JJ, Bartels-Rutten A, et al. Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study. BMC Cancer 2018;18:1006. [Crossref] [PubMed]
78. Zhang X, Eyck BM, Yang Y, Liu J, Chao YK, Hou MM, et al. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study. BMC Cancer 2020;20:194. [Crossref] [PubMed]
79. Available online: https://clinicaltrials.gov/ct2/show/NCT02551458
80. Eyck BM, van der Wilk BJ, Noordman BJ, Wijnhoven BPL, Lagarde SM, Hartgrink HH, et al. Updated protocol of the SANO trial: a stepped-wedge cluster andomized trial comparing surgery with active surveillance after neoadjuvant chemoradiotherapy for oesophageal cancer. Trials 2021;22:345. [Crossref] [PubMed]
81. Motoyama S, Sato Y, Maruyama K, Usami S, Yoshino K, Nakatsu T, Sasaki T, Wakita A, Kawakita Y, Liu J, Anbai A, Ishiyama K, Saito H, Minamiya Y. Metabolic Rather than Pathological Response to Preoperative Chemoradiotherapy Is a Stronger Predictor of Survival in cStage IIB-IV Esophageal Cancer. Anticancer Res 2017;37:4189-94. [Crossref] [PubMed]
82. Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med 2009;50:122S-50S. [Crossref] [PubMed]
83. Cremonesi M, Garibaldi C, Timmerman R, Ferrari M, Ronchi S, Grana CM, Travaini L, Gilardi L, Starzyńska A, Ciardo D, Orecchia R, Jereczek-Fossa BA, Leonardi MC. Interim (18)F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal cancer patients. A systematic review. Radiother Oncol 2017;125:200-12. [Crossref] [PubMed]
84. Moureau-Zabotto L, Touboul E, Lerouge D, Deniaud-Alexandre E, Grahek D, Foulquier JN, Petenief Y, Grès B, El Balaa H, Kerrou K, Montravers F, Keraudy K, Tiret E, Gendre JP, Grange JD, Hourry S, Talbot JN. Impact of computed tomography (CT) and 18F-deoxyglucose positron emission tomography (FDG-PET) image fusion for conformal radiotherapy in esophageal carcinoma. Cancer Radiother 2005;9:152-60. [Crossref] [PubMed]