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Huizer TJ, Lagarde SM, Nuyttens JJ, Oudijk L, Spaander MC, Valkema R, Mostert B, Wijnhoven BP, SANO- study group. Active surveillance in patients with a complete clinical response after neoadjuvant chemoradiotherapy for esophageal- and gastroesophageal junction cancer. Innov Surg Sci 2025; 10:11-19. [PMID: 40144783 PMCID: PMC11934941 DOI: 10.1515/iss-2023-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 07/30/2024] [Indexed: 03/28/2025] Open
Abstract
Neoadjuvant chemoradiotherapy in patients with esophageal- and gastroesophageal junction cancer induces tumor regression. In approximately one fourth of patients, this leads to a pathological complete response in the resection specimen. Hence, active surveillance may be an alternative strategy in patients without residual disease after neoadjuvant chemoradiotherapy. Previous studies have shown that the combination of esophagogastroduodenoscopy with bite-on-bite biopsies, endoscopic ultrasound with fine needle aspiration of suspected lymph nodes, and a PET-CT-scan can be considered adequate for the detection of residual disease. So far, it has been unclear whether active surveillance with surgery as needed is a safe treatment option and leads to non-inferior overall survival compared to standard esophagectomy after neoadjuvant chemoradiotherapy. This review will discuss the current status of active surveillance for esophageal and junctional cancer.
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Affiliation(s)
- Tamara J. Huizer
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Sjoerd M. Lagarde
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Joost J.M.E. Nuyttens
- Department of Radiation Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Lindsey Oudijk
- Department of Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Manon C.W. Spaander
- Department of Gastroenterology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Roelf Valkema
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Bianca Mostert
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Bas P.L. Wijnhoven
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - SANO- study group
- Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Radiation Oncology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Gastroenterology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands
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Pellat A, Dohan A, Soyer P, Veziant J, Coriat R, Barret M. The Role of Magnetic Resonance Imaging in the Management of Esophageal Cancer. Cancers (Basel) 2022; 14:cancers14051141. [PMID: 35267447 PMCID: PMC8909473 DOI: 10.3390/cancers14051141] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/16/2022] [Accepted: 02/18/2022] [Indexed: 02/01/2023] Open
Abstract
Esophageal cancer (EC) is the eighth more frequent cancer worldwide, with a poor prognosis. Initial staging is critical to decide on the best individual treatment approach. Current modalities for the assessment of EC are irradiating techniques, such as computed tomography (CT) and positron emission tomography/CT, or invasive techniques, such as digestive endoscopy and endoscopic ultrasound. Magnetic resonance imaging (MRI) is a non-invasive and non-irradiating imaging technique that provides high degrees of soft tissue contrast, with good depiction of the esophageal wall and the esophagogastric junction. Various sequences of MRI have shown good performance in initial tumor and lymph node staging in EC. Diffusion-weighted MRI has also demonstrated capabilities in the evaluation of tumor response to chemoradiotherapy. To date, there is not enough data to consider whole body MRI as a routine investigation for the detection of initial metastases or for prediction of distant recurrence. This narrative review summarizes the current knowledge on MRI for the management of EC.
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Affiliation(s)
- Anna Pellat
- Department of Gastroenterology and Digestive Oncology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; (A.P.); (R.C.)
- Université de Paris, 75006 Paris, France; (A.D.); (P.S.); (J.V.)
| | - Anthony Dohan
- Université de Paris, 75006 Paris, France; (A.D.); (P.S.); (J.V.)
- Department of Radiology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
| | - Philippe Soyer
- Université de Paris, 75006 Paris, France; (A.D.); (P.S.); (J.V.)
- Department of Radiology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
| | - Julie Veziant
- Université de Paris, 75006 Paris, France; (A.D.); (P.S.); (J.V.)
- Department of Digestive Surgery, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France
| | - Romain Coriat
- Department of Gastroenterology and Digestive Oncology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; (A.P.); (R.C.)
- Université de Paris, 75006 Paris, France; (A.D.); (P.S.); (J.V.)
| | - Maximilien Barret
- Department of Gastroenterology and Digestive Oncology, Hôpital Cochin, AP-HP, 27 rue du Faubourg Saint Jacques, 75014 Paris, France; (A.P.); (R.C.)
- Université de Paris, 75006 Paris, France; (A.D.); (P.S.); (J.V.)
- Correspondence:
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Accuracy of Detecting Residual Disease After Neoadjuvant Chemoradiotherapy for Esophageal Cancer: A Systematic Review and Meta-analysis. Ann Surg 2020; 271:245-256. [PMID: 31188203 DOI: 10.1097/sla.0000000000003397] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim of this study was to perform a meta-analysis on the accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) for detecting residual disease after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. SUMMARY OF BACKGROUND DATA After nCRT, one-third of patients have a pathologically complete response in the resection specimen. Before an active surveillance strategy could be offered to these patients, clinically complete responders should be accurately identified. METHODS Embase, Medline, Cochrane, and Web-of-Science were searched until February 2018 for studies on accuracy of endoscopic biopsies, EUS, or PET(-CT) for detecting locoregional residual disease after nCRT for squamous cell- or adenocarcinoma. Pooled sensitivities and specificities were calculated using random-effect meta-analyses. RESULTS Forty-four studies were included for meta-analyses. For detecting residual disease at the primary tumor site, 12 studies evaluated endoscopic biopsies, 11 qualitative EUS, 14 qualitative PET, 8 quantitative PET using maximum standardized uptake value (SUVmax), and 7 quantitative PET using percentage reduction of SUVmax (%ΔSUVmax). Pooled sensitivities and specificities were 33% and 95% for endoscopic biopsies, 96% and 8% for qualitative EUS, 74% and 52% for qualitative PET, 69% and 72% for PET-SUVmax, and 73% and 63% for PET-%ΔSUVmax. For detecting residual nodal disease, 11 studies evaluated qualitative EUS with a pooled sensitivity and specificity of 68% and 57%, respectively. In subgroup analyses, sensitivity of PET-%ΔSUVmax and EUS for nodal disease was higher in squamous cell carcinoma than adenocarcinoma. CONCLUSIONS Current literature suggests insufficient accuracy of endoscopic biopsies, EUS, and 18F-FDG PET(-CT) as single modalities for detecting residual disease after nCRT for esophageal cancer.
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Metabolic Tumor Volume Change Predicts Long-term Survival and Histological Response to Preoperative Chemotherapy in Locally Advanced Esophageal Cancer. Ann Surg 2020; 270:1090-1095. [PMID: 29727327 DOI: 10.1097/sla.0000000000002808] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
OBJECTIVE Here, we assess the ability of metabolic tumor volume (MTV) as measured by F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-FDG PET/CT) to evaluate neoadjuvant chemotherapy response for patients with locally advanced esophageal cancer (EC). BACKGROUND Optimal methods to evaluate treatment response for EC patients have not yet been established. Although previous studies have reported the value of standardized uptake value (SUV), the accuracy of predicting histological response or long-term survival in EC is limited. METHODS In all, 102 EC patients without distant metastasis who underwent F-FDG PET/CT both before and after the preoperative chemotherapy series were analyzed. RESULTS The median primary tumor MTV values before and after preoperative chemotherapy were 22.55 (range 0.4-183.1) and 2.75 (0-52.9), respectively, and the median MVT reduction rate was 86.5%. We found the most significant difference in survival between PET responders and nonresponders with a cut-off value of 60% MTV reduction, using a 10% stepwise cut-off analysis [2-year progression-free survival (PFS): 79.2 vs 44.4%; hazard ratio (HR) 3.397; P < 0.0001). With this cut-off value, histological response (P = 0.0091), tumor location (P = 0.0102), pT (P = 0.0011), and pN (P = 0.0110) were significantly associated with PET response. Univariate analysis of PFS indicated a correlation between PFS and tumor size, cT, decrease of primary lesion by CT, SUVmax reduction rate, MTV reduction rate, pT, pN, and pM. Multivariate analysis further identified pM (HR 3.063; P = 0.0279) and MTV reduction rate (HR 2.471; P = 0.0263) to be independent prognostic predictors, but not decrease of primary lesion by CT or SUVmax reduction rate. CONCLUSION MTV change is clinically useful in predicting both long-term survival and histological response to preoperative chemotherapy in EC patients, after determining the optimal cut-off value based on survival analysis.
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Cosgrove ND, Mullady DK. Endoscopic evaluation of the esophageal cancer patient after chemoradiotherapy for persistent/recurrent cancer. Dis Esophagus 2018; 31:5040371. [PMID: 29931309 DOI: 10.1093/dote/doy023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Endoscopy has an important role in the pre- and post-treatment staging of esophageal cancer. Complete pathologic response following neoadjuvant chemoradiation therapy occurs in approximately 25% of patients. However, the ability to accurately detect this preoperatively with currently available endoscopic modalities is limited such that the default pathway is for fit patients to proceed with surgical resection. This article discusses the available endoscopic modalities (primarily Esophagogastroduodenoscopy [EGD] with mucosal biopsies and endoscopic ultrasonography with or without fine needle aspiration) used for post-treatment staging of esophageal cancer. We present data regarding the benefits and limitations of endoscopic methods in assessing for residual disease. Unfortunately, endoscopic modalities are not accurate enough to identify complete pathological responsers who may avoid surgical resection.
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Affiliation(s)
- N D Cosgrove
- Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
| | - D K Mullady
- Division of Gastroenterology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA
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Wang K, Chen D, Meng Y, Xu J, Zhang Q. Clinical evaluation of 4 types of microRNA in serum as biomarkers of esophageal squamous cell carcinoma. Oncol Lett 2018; 16:1196-1204. [PMID: 29963194 DOI: 10.3892/ol.2018.8720] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Accepted: 01/06/2017] [Indexed: 12/26/2022] Open
Abstract
To the best of our knowledge, there is currently no specific biomarker for esophageal cancer used in clinical practice. However, studies consider that microRNAs (miRNAs/miRs) could have useful implications in clinical practice. The present study aimed to investigate the feasibility of using serum microRNAs as biomarkers for esophageal squamous cell carcinoma (ESCC). Using reverse transcription-quantitative polymerase chain reaction, the expression levels of serum miR-21, miR-25, miR-145 and miR-203 were detected in 31 untreated patients with ESCC (EC-UT), 35 inactive period patients with ESCC following treatment (EC-T), 33 patients with esophageal benign disease (benign) and 32 healthy donors (healthy). Furthermore, the ability of these microRNAs to function as biomarkers of ESCC alone and in combination were investigated. The expression levels of serum miR-21, miR-25 and miR-145 in EC-UT were significantly higher than in the other groups (P<0.001). High sensitivity and specificity were shown when miRNAs were used as biomarkers for ESCC, particularly miR-21 and the combination of miR-21 with miR-145. Comparing EC-UT with healthy, benign and EC-T groups, and a combined group (3 groups set as 1 negative control), the sensitivity and specificity of miR-21 were 71.0 and 96.9, 74.2 and 87.9, 77.4 and 82.9, and 74.2 and 88.0%, respectively. The combined sensitivity and specificity of miR-21 and miR-145 were 71.0 and 96.9, 90.9 and 72.7, 97.1 and 82.9, and 80.6 and 80.0%, respectively. In conclusion, 3 types of miRNA (miR-21, miR-25 and miR-145) in serum could serve as potential biomarkers for ESCC. Furthermore, the expression level of miR-145 in serum was upregulated, compared with the downregulation reported in previous studies in ESCC tissues and cells.
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Affiliation(s)
- Kai Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Dongmei Chen
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Yue Meng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Jianjun Xu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
| | - Qingyun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Clinical Laboratory, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China
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Park IH, Kim JY. Surveillance or resection after chemoradiation in esophageal cancer. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:82. [PMID: 29666805 DOI: 10.21037/atm.2017.12.16] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The treatment of locally advanced esophageal cancer continues to evolve. Previously, surgery was considered the foundation of treatment, but chemoradiation (CRT) has taken on a larger role both in the neoadjuvant setting and as definitive treatment. It has become clear that although some patients benefit from esophagectomy after CRT, a large subset of patients likely derive no benefit, and may be harmed by surgery. Some patients are cured from CRT alone and therefore do not need surgery. Another group of patients likely have metastatic disease at the time of local therapy that is just undetected on imaging and also do not benefit from surgery. A third group of patients will have persistent locoregional disease only after CRT. This last group is the subset who will actually benefit from surgery, but this likely comprises only a minority of patients with locally advanced disease. A strategy to maximize survival while minimizing unnecessary surgery is a reasonable goal, but present technology does not allow us to do this with certainty. Thus, the decision of whether to pursue resection or surveillance after CRT can be difficult as clinicians and patients try to balance the goal of maximizing the likelihood of cure against the risk of surgery and its impact on quality of life.
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Affiliation(s)
- Il-Hwan Park
- Department of Chest Surgery, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Jae Y Kim
- Division of Thoracic Surgery, City of Hope Cancer Center, Duarte, CA, USA
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Gerbaudo VH, Killoran JH, Kim CK, Hornick JL, Nowak JA, Enzinger PC, Mamon HJ. Pilot study of serial FLT and FDG-PET/CT imaging to monitor response to neoadjuvant chemoradiotherapy of esophageal adenocarcinoma: correlation with histopathologic response. Ann Nucl Med 2018; 32:165-174. [PMID: 29332233 DOI: 10.1007/s12149-018-1229-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Accepted: 01/04/2018] [Indexed: 11/27/2022]
Abstract
OBJECTIVE The aim of this prospective pilot study was to investigate the potential of serial FLT-PET/CT compared to FDG-PET/CT to provide an early indication of esophageal cancer response to concurrent neoadjuvant chemoradiation therapy. METHODS Five patients with biopsy-proven esophageal adenocarcinomas underwent neoadjuvant chemoradiation (Tx) prior to minimally invasive esophagectomy. The presence of residual tumor was classified histologically using the Mandard et al. criteria, categorizing patients as pathologic responders and non-responders. Participants underwent PET/CT imaging 1 h after intravenous administration of FDG and of FLT on two separate days within 48 h of each other. Each patient underwent a total of 3 scan "pairs": (1) pre-treatment, (2) during treatment, and (3) post-treatment. Image-based response to therapy was measured in terms of changes in SUVmax (ΔSUV) between pre- and post-therapeutic FLT- and FDG-PET scans. The PET imaging findings were correlated with the pathology results after surgery. RESULTS All tumors were FDG and FLT avid at baseline. Lesion FLT uptake was lower than with FDG. Neoadjuvant chemoradiation resulted in a reduction of tumor uptake of both radiotracers in pathological responders (n = 3) and non-responders (n = 2). While the difference in the reduction in mean tumor FLT uptake during Tx between responders (ΔSUV = - 55%) and non-responders (ΔSUV = - 29%) was significant (P = 0.007), for FDG it was not, [responders had a mean ΔSUV = - 39 vs. - 31% for non-responders (P = 0.74)]. The difference in the reduction in tumor FLT uptake at the end of treatment between responders (ΔSUV = - 62%) and non-responders (ΔSUV = - 57%) was not significant (P = 0.54), while for FDG there was a trend toward significance [ΔSUV of responders = - 74 vs. - 52% in non-responders (P = 0.06)]. CONCLUSION The results of this prospective pilot study suggest that early changes in tumor FLT uptake may be better than FDG in predicting response of esophageal adenocarcinomas to neoadjuvant chemoradiation. These preliminary results support the need to corroborate the value of FLT-PET/CT in a larger cohort.
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Affiliation(s)
- Victor H Gerbaudo
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, USA.
| | - Joseph H Killoran
- Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Chun K Kim
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts, USA
| | - Jason L Hornick
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Jonathan A Nowak
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
| | - Peter C Enzinger
- Center for Esophageal and Gastric Cancer, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
| | - Harvey J Mamon
- Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
- Center for Esophageal and Gastric Cancer, Dana Farber Cancer Institute, Harvard Medical School, Boston, USA
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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; 162:836-845. [PMID: 28711321 DOI: 10.1016/j.surg.2017.06.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2017] [Revised: 06/02/2017] [Accepted: 06/06/2017] [Indexed: 10/19/2022]
Abstract
BACKGROUND There is no consensus strategy for treatment of T4 esophageal cancer, and because of this, a better evaluation of treatment response is crucial to establish personalized therapies. This study aimed to establish a useful system for evaluating treatment response in T4 esophageal cancer. METHODS This study included 130 patients with cT4 esophageal cancer without distant metastasis who underwent 18F-fluorodeoxyglucose-positron emission tomography before and after a series of induction treatments comprising chemoradiation or chemotherapy. We evaluated the maximal standardized uptake value and treatment response. RESULTS The mean ± standard deviation of standardized uptake value in the primary tumor before and after induction treatments were 13.8 ± 4.4 and 5.4 ± 4.1, respectively, and the mean standardized uptake value decrease was 58.4%. The most significant difference in survival between positron emission tomography-primary tumor responders and nonresponders was at a decrease of 60% standardized uptake value, based on every 10% stepwise cutoff analysis (2-year cause-specific survival: 60.2 vs 23.5%; hazard ratio = 2.705; P < .0001). With this cutoff value, the resectability (P = .0307), pathologic response (P = .0004), and pT stage (P < .0001) were associated with positron emission tomography-primary tumor response. Univariate analysis of 2-year cause-specific survival indicated a correlation between cause-specific survival and clinical stages according to TNM classification, esophageal perforation, positron emission tomography-primary tumor response, lymph node status evaluated by positron emission tomography before and after induction treatments, and operative resection. Multivariate analysis further identified positron emission tomography-primary tumor response (hazard ratio = 2.354; P = .0107), lymph node status evaluated by positron emission tomography after induction treatments (hazard ratio = 1.966; P = .0089), and operative resection (hazard ratio = 2.012; P = .0245) as independent prognostic predictors. CONCLUSION Positron emission tomography evaluation of the response of primary and metastatic lesions to induction treatments is important to formulate treatment strategies for cT4 esophageal cancer.
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Affiliation(s)
- Tomoki Makino
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
| | - Makoto Yamasaki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Koji Tanaka
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Mitsuaki Tatsumi
- Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shuji Takiguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Jun Hatazawa
- Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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Persistent Dysphagia After Induction Chemotherapy in Patients with Esophageal Adenocarcinoma Predicts Poor Post-Operative Outcomes. J Gastrointest Cancer 2016; 48:181-189. [PMID: 27734205 DOI: 10.1007/s12029-016-9881-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
PURPOSE Preoperative therapy is frequently employed in the management of esophageal adenocarcinoma. However, many patients are found to have advanced pathologic stage and have poor outcomes. A prognostic factor which identifies this patient population before surgery would be desirable, as alternative treatment strategies may be warranted. METHODS Between 2/08 and 1/12, 60 evaluable patients with locally advanced esophageal adenocarcinoma enrolled in single-arm phase II trial of induction chemotherapy, surgery, and post-operative adjuvant chemo-radiotherapy (CRT). A clinical stage of T3, N1, or M1a (AJCC 6th) was required for eligibility. Induction chemotherapy with epirubicin 50 mg/m2 d1, oxaliplatin 130 mg/m2 d1, and fluorouracil 200 mg/m2/day continuous infusion for 3 weeks, was given every 21 days for 3 cycles and was followed by surgical resection. Adjuvant CRT consisted of 50-55 Gy @ 1.8-2.0 Gy/day and 2 cycles of cisplatin (20 mg/m2/day) and fluorouracil (1000 mg/m2/day) given as 96-h infusions during weeks 1 and 4 of radiotherapy. Dysphagia was assessed at baseline and after induction chemotherapy. RESULTS Persistent dysphagia was associated with worse distant metastatic control [HR 3.48 (1.43-8.43), p = 0.006], recurrence free survival [HR 3.04 (1.34-6.92), p = 0.008], and overall survival [HR 3.31 (1.43-7.66), p = 0.005]. Persistent dysphagia was associated with more advanced pathologic T descriptor (pT) (p = 0.048) and N descriptor (pN) (p = 0.002), a greater median number of involved lymph nodes (3 v 1, p = 0.003), and greater residual tumor viability (p = 0.05). No patients with persistent dysphagia had pT0-T2 or pN0 disease. CONCLUSIONS Persistent dysphagia after induction chemotherapy is associated with more advanced pathologic stage and inferior outcomes.
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The 100 most cited articles investigating the radiological staging of oesophageal and junctional cancer: a bibliometric analysis. Insights Imaging 2016; 7:619-28. [PMID: 27278388 PMCID: PMC4956630 DOI: 10.1007/s13244-016-0505-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 05/18/2016] [Accepted: 05/24/2016] [Indexed: 12/15/2022] Open
Abstract
Objectives Accurate staging of oesophageal cancer (OC) is vital. Bibliometric analysis highlights key topics and publications that have shaped understanding of a subject. The 100 most cited articles investigating radiological staging of OC are identified. Methods The Thomas Reuters Web of Science database with search terms including “CT, PET, EUS, oesophageal and gastro-oesophageal junction cancer” was used to identify all English language, full-script articles. The 100 most cited articles were further analysed by topic, journal, author, year and institution. Results A total of 5,500 eligible papers were returned. The most cited paper was Flamen et al. (n = 306), investigating the utility of positron emission tomography (PET) for the staging of patients with potentially operable OC. The most common research topic was accuracy of staging investigations (n = 63). The article with the highest citation rate (38.00), defined as the number of citations divided by the number of complete years published, was Tixier et al. investigating PET texture analysis to predict treatment response to neo-adjuvant chemo-radiotherapy, cited 114 times since publication in 2011. Conclusion This bibliometric analysis has identified key publications regarded as important in radiological OC staging. Articles with the highest citation rates all investigated PET imaging, suggesting this modality could be the focus of future research. Main Messages • This study identifies key articles that investigate radiological staging of oesophageal cancer. • The most common topic was accuracy of staging investigations. • The article with the highest citation rate investigated the use of texture analysis in PET images.
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van Rossum PSN, Goense L, Meziani J, Reitsma JB, Siersema PD, Vleggaar FP, van Vulpen M, Meijer GJ, Ruurda JP, van Hillegersberg R. Endoscopic biopsy and EUS for the detection of pathologic complete response after neoadjuvant chemoradiotherapy in esophageal cancer: a systematic review and meta-analysis. Gastrointest Endosc 2016; 83:866-79. [PMID: 26632523 DOI: 10.1016/j.gie.2015.11.026] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 11/15/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Accurate determination of residual cancer status after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer could assist in selecting the optimal treatment strategy. The aim of this study was to review the evidence on the diagnostic accuracy of endoscopic biopsy and EUS after nCRT for detecting residual cancer at the primary tumor site (ypT+) and regional lymph nodes (ypN+) as opposed to a pathologic complete response (ypT0 and ypN0). METHODS PubMed/Medline, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies reporting on the accuracy of endoscopic biopsy or EUS in detecting residual cancer versus complete response after nCRT for esophageal cancer with histopathology as the reference standard. Bivariate random-effects models were used to estimate pooled sensitivities and specificities and examine sources of heterogeneity. RESULTS Twenty-three studies comprising 12 endoscopic biopsy studies (1281 patients), 11 EUS studies reporting on ypT status (593 patients), and 10 EUS studies reporting on ypN status (602 patients), were included. Pooled estimates for sensitivity of endoscopic biopsy after nCRT for predicting ypT+ were 34.5% (95% confidence interval [CI], 26.0%-44.1%) and for specificity 91.0% (95% CI, 85.6%-94.5%). Pooled estimates for sensitivity of EUS after nCRT were 96.4% (95% CI, 91.7%-98.5%) and for specificity were 10.9% (95% CI, 3.5%-29.0%) for detecting ypT+, and 62.0% (95% CI, 46.0%-75.7%) and 56.7% (95% CI, 41.8%-70.5%) for detecting ypN+, respectively. CONCLUSIONS Endoscopic biopsy after nCRT is a specific but not sensitive method for detecting residual esophageal cancer. Although EUS after nCRT yields a high sensitivity, only a limited number of patients will have negative findings at EUS with still a substantial false-negative rate. Furthermore, EUS provides only moderate accuracy for detecting residual lymph node involvement. Based on these findings, these endoscopic modalities cannot be used to withhold surgical treatment in test-negative patients after nCRT. ( CLINICAL TRIAL REGISTRATION NUMBER CRD42015016527.).
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Affiliation(s)
- Peter S N van Rossum
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Lucas Goense
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jihane Meziani
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Johannes B Reitsma
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marco van Vulpen
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Gert J Meijer
- Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jelle P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
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Litle VR. Staging Techniques for Carcinoma of the Esophagus. SABISTON AND SPENCER SURGERY OF THE CHEST 2016:645-656. [DOI: 10.1016/b978-0-323-24126-7.00037-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Bohle W, Kasper M, Zoller WG. Different accuracy of endosonographic tumor staging after neoadjuvant chemotherapy and chemoradiotherapy in esophageal cancer. Surg Endosc 2015; 30:2922-8. [PMID: 26487231 DOI: 10.1007/s00464-015-4578-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 09/19/2015] [Indexed: 12/17/2022]
Abstract
BACKGROUND Treatment response to neoadjuvant therapy is histologically associated with more or less intensive inflammation and fibrosis. In consequence, accuracy of endosonographic TN-tumor staging after neoadjuvant treatment is hampered. We analyzed whether the kind of treatment chosen [chemoradiotherapy (CRT) or chemotherapy (CT)] differently influences the accuracy of endoscopic ultrasound after neoadjuvant therapy in esophageal cancer. METHODS We performed serial endoscopic ultrasound examinations in 18 patients after neoadjuvant CRT and 30 patients after neoadjuvant CT. TN-stage was classified according to the standard parameter. Histological examination of the surgical resection specimen served as gold standard. RESULTS The most frequent error was overstaging, especially in patients with complete tumor response or minimal residual disease. Accuracy of T-staging was significantly worse after CRT (0.16) than after CT (0.43), obviously due to difficulty in distinguishing residual tumor from treatment-associated fibrosis and inflammation. Accuracy of N-staging was also hampered, but to a less extent (sensitivity/specificity 0.85/0.36 after CRT, and 0.5/0.42 after CT). CONCLUSIONS Accuracy of endosonographic TN-tumor staging is significantly more hampered by neoadjuvant CRT than after CT. However, endoscopic ultrasound is insufficient for TN-staging irrespective of the kind of neoadjuvant therapy performed.
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Affiliation(s)
- Wolfram Bohle
- Department of Gastroenterology, Katharinenhospital, Klinikum Stuttgart, Kriegsbergstr. 60, 70174, Stuttgart, Germany
| | - Michaela Kasper
- Department of Gastroenterology, Katharinenhospital, Klinikum Stuttgart, Kriegsbergstr. 60, 70174, Stuttgart, Germany
| | - Wolfram G Zoller
- Department of Gastroenterology, Katharinenhospital, Klinikum Stuttgart, Kriegsbergstr. 60, 70174, Stuttgart, Germany.
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Monitoring the early biologic response of esophageal carcinoma after irradiation with 18F-FLT: an in-vitro and in-vivo study. Nucl Med Commun 2015; 35:1212-9. [PMID: 25192190 DOI: 10.1097/mnm.0000000000000201] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of our study was to explore the value of 3'-deoxy-3'-[F]fluorothymidine (F-FLT) and F-FLT PET in monitoring the early biologic response of esophageal carcinoma after irradiation in vitro and in vivo. METHODS After 2, 4, and 8 h of irradiation at different doses (0, 5, 10, and 15 Gy) of esophageal carcinoma cells in vitro, the uptake ratio of F-FLT, the relative cell survival rate, and ATP levels were measured. The tumor uptake ratio of F-FLT [tumor-to-nontumor (T/NT)] was measured through PET scans before and on the first, seventh, and 15th day after irradiation. The expression of proliferating cell nuclear antigen and Ki-67 was determined in both untreated and treated tumors. RESULTS Compared with the control group, the uptake ratio changes of F-FLT after 2 h of irradiation with 5 Gy showed no statistical significance (3.65±0.17 vs. 4.00±0.17%, P>0.05), whereas the uptake ratios of the other groups decreased notably (F=33.93, P<0.01). The differences in the relative survival rates were not statistically significant (F=4.02, P>0.05). Linear regression analysis indicated a significant correlation between F-FLT and ATP levels (r=0.89, P<0.01). On F-FLT PET scan images of the xenografts, the baseline uptake ratio (T/NT) was 2.24±0.06. It decreased to 1.99±0.09, 1.85±0.04, and 1.15±0.10 at 1, 7, and 15 days after irradiation with 10 Gy. Tumor uptake of F-FLT was closely correlated with proliferating cell nuclear antigen and Ki-67 expressions (r=0.83, P<0.001, and r=0.88, P<0.001). CONCLUSION The uptake changes of F-FLT in esophageal carcinoma cells and tumor xenografts may reflect the early biological response of esophageal carcinoma after irradiation. Thus, F-FLT PET may be potentially used to monitor the early response of esophageal carcinoma after radiotherapy.
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Khanna LG, Gress FG. Preoperative evaluation of oesophageal adenocarcinoma. Best Pract Res Clin Gastroenterol 2015; 29:179-91. [PMID: 25743465 DOI: 10.1016/j.bpg.2014.12.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2014] [Accepted: 12/23/2014] [Indexed: 01/31/2023]
Abstract
The preoperative evaluation of oesophageal adenocarcinoma involves endoscopic ultrasound (EUS), computed tomography (CT), and positron emission tomography (PET). With routine Barrett's oesophagus surveillance, superficial cancers are often identified. EUS, CT and PET have a limited role in the staging of superficial tumours. Standard EUS has limited accuracy, but high frequency ultrasound miniprobes are valuable for assessing tumour stage in superficial tumours. However, the best method for determining depth of invasion, and thereby stage of disease, is endoscopic mucosal resection. In contrast, in advanced oesophageal cancers, a multi-modality approach is crucial. Accurate tumour staging is very important since the treatment of advanced cancers involves a combination of chemotherapy, radiation, and surgery. EUS is very useful for staging of the tumour and nodes. High frequency ultrasound miniprobes provide the ability to perform staging when the lesion is obstructing the oesophageal lumen. CT and PET provide valuable information regarding node and metastasis staging.
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Affiliation(s)
- Lauren G Khanna
- Division of Digestive & Liver Diseases, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA.
| | - Frank G Gress
- Division of Digestive & Liver Diseases, Columbia University Medical Center, 161 Fort Washington Avenue, Herbert Irving Pavilion 13, New York, NY 10032, USA.
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17
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Patched targeting peptides for imaging and treatment of hedgehog positive breast tumors. BIOMED RESEARCH INTERNATIONAL 2014; 2014:525680. [PMID: 25276795 PMCID: PMC4172929 DOI: 10.1155/2014/525680] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2014] [Revised: 07/11/2014] [Accepted: 07/15/2014] [Indexed: 11/22/2022]
Abstract
High tumor hedgehog expression is correlated with poor prognosis in invasive ductal carcinoma. Peptides which bind the patched receptor have recently been reported to have a growth inhibitory effect in tumors with activated hedgehog signaling. We sought to examine growth inhibition with these peptides in breast cancer cells and use these peptides as molecular imaging probes to follow changes in hedgehog expression after chemotherapy. Significant growth inhibition was observed in breast cancer cell lines treated with PTCH-blocking peptides. Significant in vitro uptake was observed with both FITC- and 99mTc-EC-peptide conjugates. In vivo imaging studies displayed greater accumulation of 99mTc-labeled peptides within tumors as compared to adjacent muscle tissue. Patched receptor expression increased after treatment and this correlated with an increase in tumor radiotracer uptake. These studies suggest that peptides which bind the sonic hedgehog docking site in patched receptor correlate with patched expression and can be used to image patched in vivo. Further, our data suggest that radiolabeled peptides may enable us to examine the activity of the hedgehog signaling pathway and to evaluate response to anti-cancer therapies.
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18
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Shim CN, Song MK, Lee HS, Chung H, Lee H, Shin SK, Lee SK, Lee YC, Park JC. Prediction of survival by tumor area on endosonography after definitive chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus. Digestion 2014; 90:98-107. [PMID: 25196528 DOI: 10.1159/000365073] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2013] [Accepted: 06/04/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND Definitive chemoradiotherapy (CRT) is a reasonable approach for patients with locally advanced esophageal cancer who are not surgical candidates. This study was performed to investigate whether endosonography (EUS) assessment of tumor area response is a useful prognostic marker in patients with squamous cell carcinoma (SCC) of the esophagus who receive definitive CRT. METHODS A total of 33 patients who received definitive CRT for locally advanced esophageal SCC were enrolled. The maximal transverse cross-sectional area of the tumor was measured before and after definitive therapy. EUS response was defined as a ≥50% reduction of the tumor area after definitive CRT. RESULTS Based on EUS evaluation, there were 20 nonresponders (60.6%) and 13 responders (39.4%). The median progression-free survival (PFS) was significantly longer in EUS responders than EUS nonresponders (p = 0.005). However, there was no statistical significance in overall survival according to EUS response (p = 0.120). During multivariate analysis, EUS response to definitive CRT was the only significant factor associated with PFS (p = 0.045), whereas EUS response to definitive CRT was not associated with overall survival (p = 0.221). CONCLUSIONS A reduction of the maximal cross-sectional tumor area measured by EUS correlates with a superior prognosis in patients with locally advanced SCC of the esophagus after definitive CRT.
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Affiliation(s)
- Choong Nam Shim
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
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19
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A phase II trial of induction epirubicin, oxaliplatin, and fluorouracil, followed by surgery and postoperative concurrent cisplatin and fluorouracil chemoradiotherapy in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction. J Thorac Oncol 2014; 9:1561-7. [PMID: 25170643 DOI: 10.1097/jto.0000000000000312] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
INTRODUCTION Preoperative chemoradiotherapy improves local control in patients with locoregionally advanced adenocarcinoma of the esophagus and gastroesophageal junction (GEJ). Distant failure remains common, however, suggesting potential benefit from additional chemotherapy. This phase II study investigated the addition of induction chemotherapy to surgery and adjuvant chemoradiotherapy. METHODS Patients with cT3-4 or N1 or M1a (American Joint Committee on Cancer 6th edition) adenocarcinoma of the esophagus and GEJ were eligible. Induction chemotherapy, with epirubicin 50 mg/m/d, oxaliplatin 130 mg/m/d, and fluorouracil 200 mg/m/d continuous infusion for 3 weeks, was given every 21 days for three courses, followed by surgery. Adjuvant chemoradiotherapy consisted of 50 to 55 Gy at 1.8 to 2.0 Gy/d and two courses of cisplatin (20 mg/m/d) and fluorouracil (1000 mg/m/d) during weeks 1 and 4 of radiotherapy. RESULTS Between February 2008 and January 2012, 60 evaluable patients enrolled. Resection was accomplished in 54 patients (90%) and adjuvant chemoradiotherapy in 48 (80%) patients. Toxicity included unplanned hospitalization in 18% of patients during induction chemotherapy and 19% of patients during adjuvant chemoradiotherapy. There was one chemotherapy-related and two postoperative deaths. With a median follow-up of 43 months, the projected 3-year locoregional control is 88%, distant metastatic control 46%, relapse-free survival 41%, and overall survival 47%. Symptomatic response to chemotherapy and the percentage of remaining viable tumor at surgery proved the strongest predictors of survival and distant control. CONCLUSIONS Chemotherapy, surgery, and adjuvant chemoradiotherapy are feasible and produce outcomes similar to other multimodality treatment schedules in locoregionally advanced adenocarcinoma of the esophagus and GEJ. Symptomatic response and less residual tumor at surgery were associated with improved outcomes.
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Sun F, Chen T, Han J, Ye P, Hu J. Staging accuracy of endoscopic ultrasound for esophageal cancer after neoadjuvant chemotherapy: a meta-analysis and systematic review. Dis Esophagus 2014; 28:757-71. [PMID: 25168285 DOI: 10.1111/dote.12274] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This study aims to evaluate the accuracy of endoscopic ultrasound (EUS) in the staging of esophageal cancer after neoadjuvant chemotherapy (NAC). Articles were searched in Medline, Pubmed, Cochrane Database of Systemic Reviews, Google scholar, and EMBASE. Two reviewers independently searched and extracted data. Meta-analysis of the accuracy of EUS was analyzed by calculating pooled estimates of sensitivity, specificity, likelihood ratios (LR), and diagnostic odds ratio (DOR). Pooling was conducted using either fixed-effects model or random-effects model depending on the heterogeneity across studies. Sixteen studies (n = 724) were included in this analysis. The pooled sensitivity and specificity of EUS to diagnose T1 stage tumor was 23% (95% confidence interval [CI] 16-32%) and 95% (95%CI 93-97%), respectively. For T2 stage, EUS had a pooled sensitivity and specificity of 29% (95%CI 19-41%) and 84% (95%CI 77-88%). The pooled sensitivity and specificity of EUS were 81% (95%CI 72-88%) and 42% (95%CI 33-52%) in determining T3 stage tumor. To diagnose T4 stage tumor, EUS had a pooled sensitivity of 43% (95%CI 31-56%) and specificity of 96% (95%CI 94-97%), respectively. In determining N stage, the pooled sensitivity and specificity of EUS were 69% (95%CI 58-79%) and 52% (95%CI 42-62%). EUS is a moderately accurate technique in staging esophageal cancer after NAC. Its sensitivity is relatively high in T3 while specificity is high in other T stages (T1, T2, and T4). Tumors restaged by EUS as T4 should not be assigned to surgery because it is very likely to be inoperable. EUS is not reliable for N staging with its poor sensitivity and specificity. Subgroup analysis shows that staging accuracy did not improve with time.
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Affiliation(s)
- F Sun
- Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - T Chen
- Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - J Han
- Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - P Ye
- Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - J Hu
- Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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21
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Eil RL, Thomas CR. New methodology, tools, and protocolized analysis are needed to advance individualized treatment paradigms in esophageal cancer. Dis Esophagus 2014; 27:360-1. [PMID: 24592977 DOI: 10.1111/dote.12211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- R L Eil
- Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
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Kim JY, Hofstetter WL. Esophagectomy after chemoradiation: who and when to operate. Semin Thorac Cardiovasc Surg 2013; 24:288-93. [PMID: 23465677 DOI: 10.1053/j.semtcvs.2012.10.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2012] [Indexed: 11/11/2022]
Abstract
Neoadjuvant chemoradiation is the standard of care for locally advanced esophageal cancer. After completion of chemoradiotherapy, deciding which patients benefit from surgery remains a challenge. For patients who decide on surgery, the optimal timing is unknown. The complexity of these questions requires an individualized approach, taking into account the expertise of the surgeon, the condition of the patient, and the biology of the tumor.
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Affiliation(s)
- Jae Y Kim
- Division of Thoracic Surgery, City of Hope Cancer Center, Duarte, California, USA
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23
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Khangura SK, Greenwald BD. Endoscopic management of esophageal cancer after definitive chemoradiotherapy. Dig Dis Sci 2013; 58:1477-85. [PMID: 23325163 DOI: 10.1007/s10620-012-2554-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2012] [Accepted: 12/24/2012] [Indexed: 01/29/2023]
Abstract
BACKGROUND Concurrent chemoradiotherapy (CRT) is a potentially curative non-surgical option for locally advanced esophageal cancer, with pathological complete response (CR) ranging from 13 to 49 %. The rate of persistent and recurrent disease within the esophagus remains high at 40-60 %, and treatment of these tumors may improve disease-free survival. The aim of this review is to assess the efficacy of salvage endoscopic therapies for recurrent esophageal cancer. METHODS Medline and Embase were searched for relevant studies published in the English-language literature that reported use of endoscopic modalities, including photodynamic therapy (PDT), endoscopic mucosal resection (EMR), and spray cryotherapy, as salvage therapies for esophageal cancer. RESULTS A total of 12 studies were identified. In small case series of PDT, CR varied from 20 to 100 %, with 1-, 3-, and 5-year overall survival rates of 65-80, 34-47, and 36 %, respectively. Data from three studies of EMR in squamous cell cancer show CR in 50 % of cases, with 3- and 5-year overall survival of 56-81 and 49 %, respectively. Endoscopic spray cryotherapy has recently been used in this setting with an observed CR of 37.5 %. CONCLUSIONS Endoscopic salvage therapies are options for those patients with disease limited to the superficial esophageal wall and those who are unfit to undergo salvage esophagectomy. Widespread application of endoscopic salvage therapies is limited by the lack of awareness and guidelines for endoscopic surveillance post-CRT and limited data on the effectiveness of endoscopic therapies.
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Affiliation(s)
- Sajneet K Khangura
- Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
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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. [PMID: 23613667 PMCID: PMC3629360 DOI: 10.4143/crt.2013.45.1.22] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2012] [Accepted: 01/06/2013] [Indexed: 12/22/2022] Open
Abstract
Purpose Parameters of positron emission tomography-computed tomography (PET-CT) were compared with the results of histopathologic examination in order to determine which can provide an objective indication of response after neoadjuvant chemoradiation for treatment of thoracic esophageal squamous cell carcinoma (SCC). Materials and Methods Between August 2003 and January 2010, data on 25 patients who underwent neoadjuvant chemoradiation and subsequent resection for treatment of esophageal SCC were retrospectively reviewed. Changes in maximum standardized uptake value (ΔSUVmax), metabolic tumor volume (ΔMTV), and total lesion glycolysis (ΔTLG) were analyzed by comparison with the histopathologic findings. Results Pathologic complete remission (CR) for the main tumor was achieved in 11 patients. Postradiation esophagitis was observed in 10 patients. ΔSUVmax of the main tumor was significantly greater in the CR group than in the partial response (PR) group (p=0.039), while ΔMTV and ΔTLG of the main tumor were not (p=0.141 and p=0.349, respectively). The cut-off ΔSUVmax value for CR was estimated as 72.1%, indicating significantly better accuracy than visual interpretation (p=0.045). Of the 48 involved lymph nodes, ΔSUVmax and ΔMTV of lymph nodes were significantly greater in the CR group than in the PR group (p=0.045 and p=0.014, respectively), while ΔTLG was not (p=0.063). The cut-off value of ΔSUVmax for prediction of CR in lymph nodes was calculated as 50.67%. Conclusion PET-CT could be used for prediction of response to neoadjuvant treatment in thoracic esophageal SCC. ΔSUVmax may be a more significant predictor for CR after neoadjuvant chemoradiation than ΔTLG and ΔMTV.
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Affiliation(s)
- Joon Suk Park
- Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Evans JA, Early DS, Chandraskhara V, Chathadi KV, Fanelli RD, Fisher DA, Foley KQ, Hwang JH, Jue TL, Pasha SF, Sharaf R, Shergill AK, Dominitz JA, Cash BD. The role of endoscopy in the assessment and treatment of esophageal cancer. Gastrointest Endosc 2013; 77:328-34. [PMID: 23410694 DOI: 10.1016/j.gie.2012.10.001] [Citation(s) in RCA: 94] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2012] [Accepted: 10/01/2012] [Indexed: 02/08/2023]
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Imaging strategies in the management of oesophageal cancer: what's the role of MRI? Eur Radiol 2013; 23:1753-65. [PMID: 23404138 DOI: 10.1007/s00330-013-2773-6] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2012] [Revised: 12/07/2012] [Accepted: 12/16/2012] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To outline the current role and future potential of magnetic resonance imaging (MRI) in the management of oesophageal cancer regarding T-staging, N-staging, tumour delineation for radiotherapy (RT) and treatment response assessment. METHODS PubMed, Embase and the Cochrane library were searched identifying all articles related to the use of MRI in oesophageal cancer. Data regarding the value of MRI in the areas of interest were extracted in order to calculate sensitivity, specificity, predictive values and accuracy for group-related outcome measures. RESULTS Although historically poor, recent improvements in MRI protocols and techniques have resulted in better imaging quality and the valuable addition of functional information. In recent studies, similar or even better results have been achieved using optimised MRI compared with other imaging strategies for T- and N-staging. No studies clearly report on the role of MRI in oesophageal tumour delineation and real-time guidance for RT so far. Recent pilot studies showed that functional MRI might be capable of predicting pathological response to treatment and patient prognosis. CONCLUSIONS In the near future MRI has the potential to bring improvement in staging, tumour delineation and real-time guidance for RT and assessment of treatment response, thereby complementing the limitations of currently used imaging strategies. KEY POINTS • MRI's role in oesophageal cancer has been somewhat limited to date. • However MRI's ability to depict oesophageal cancer is continuously improving. • Optimising TN-staging, radiotherapy planning and response assessment ultimately improves individualised cancer care. • MRI potentially complements the limitations of other imaging strategies regarding these points.
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Évolution des cancers de l’œsophage : impact de la stratégie thérapeutique. Cancer Radiother 2013; 17:10-20. [DOI: 10.1016/j.canrad.2012.10.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Revised: 10/17/2012] [Accepted: 10/22/2012] [Indexed: 12/25/2022]
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Klayton T, Li T, Yu JQ, Keller L, Cheng J, Cohen SJ, Meropol NJ, Scott W, Xu-Welliver M, Konski A. The Role of Qualitative and Quantitative Analysis of F18-FDG Positron Emission Tomography in Predicting Pathologic Response Following Chemoradiotherapy in Patients with Esophageal Carcinoma. J Gastrointest Cancer 2012; 43:612-8. [DOI: 10.1007/s12029-012-9412-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Griffin JM, Reed CE, Denlinger CE. Utility of restaging endoscopic ultrasound after neoadjuvant therapy for esophageal cancer. Ann Thorac Surg 2012; 93:1855-9; discussion 1860. [PMID: 22516835 DOI: 10.1016/j.athoracsur.2011.12.095] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Revised: 12/14/2011] [Accepted: 12/19/2011] [Indexed: 12/26/2022]
Abstract
BACKGROUND Currently, the most accurate staging test for patients with esophageal cancer is endoscopic ultrasound (EUS). At many institutions, patients who have completed neoadjuvant chemotherapy and radiotherapy for esophageal cancer undergo restaging EUS before proceeding to surgical resection. The benefit of this restaging procedure remains controversial. METHODS We retrospectively studied consecutive patients who had pre-resection restaging EUS after receiving neoadjuvant treatment to assess accuracy of EUS restaging and determine whether it predicted survival. RESULTS Final pathologic data were available for 73 patients who underwent restaging EUS (3 patients had missing T or N stage at one time point). Median time from restaging EUS to resection was 20 days. Restaging EUS accurately predicted pathologic T status in 26 of 72 patients (36%), N status in 44 of 71 (62%), and detected a complete pathologic response in 2 of 19 (10.5%). EUS inappropriately classified 10 patients as T0 N0. Agreement between EUS and pathologic staging was poor for T (κ=0.14) and N status (κ=0.24). Median time from resection to death or last follow-up was 20 months. Pathologic T and N status were each significant predictors of survival (p=0.049 and p=0.0004, respectively). There were nonsignificant trends toward better survival for lower EUS T (p=0.32) and N status (p=0.0946). CONCLUSIONS Restaging by EUS before resection did not accurately predict pathologic stage in patients with esophageal cancer who received neoadjuvant treatment. As a result of this investigation, our institution no longer routinely performs restaging EUS.
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Affiliation(s)
- Jeffrey M Griffin
- Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA
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Owaki T, Matsumoto M, Okumura H, Uchicado Y, Kita Y, Setoyama T, Sasaki K, Sakurai T, Omoto I, Shimada M, Sakamoto F, Yoshinaka H, Ishigami S, Ueno S, Natsugoe S. Endoscopic ultrasonography is useful for monitoring the tumor response of neoadjuvant chemoradiation therapy in esophageal squamous cell carcinoma. Am J Surg 2012; 203:191-7. [DOI: 10.1016/j.amjsurg.2011.01.027] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2010] [Revised: 01/21/2011] [Accepted: 01/21/2011] [Indexed: 11/29/2022]
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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. [PMID: 21892034 DOI: 10.1097/rlu.0b013e318219b0c0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE To analyze the predictive value of fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake using positron emission tomography and computed tomography to assess the outcome of definitive chemoradiation in nonsurgical esophageal squamous cell carcinoma. MATERIALS AND METHODS A retrospective review of 61 patients with clinical stage T1-4, N0/1, and M0 was performed. Chemoradiation included chemotherapy with fluorouracil plus cisplatin and irradiation with a total dose of 5600 to 6400 centigray (cGy). Positron emission tomography combined with computed tomography scans were acquired before and during the therapy. The correlation between a decrease in FDG uptake and 5-year progression-free survival (PFS) was analyzed by a receiver operating characteristic curve method to determine a cutoff value. A 5-year overall survival (OS), PFS, and cancer-specific survival (CSS) were evaluated by Kaplan-Meier method. RESULTS The mean of standardized uptake value decreased significantly during chemoradiation (P = 0.001). Using 51% reduction of FDG uptake as a cutoff value provided a sensitivity of 76.9% and a specificity of 79.2% in predicting PFS (P = 0.000). The positive predictive value and negative predictive value were 50% and 95%, respectively. PFS, CSS, and OS were significantly different when grouped by this cutoff value (P < 0.05), and when dichotomized by stage T1-2 and T3-4 (P < 0.05), simultaneously with a decrease of 51% or more in FDG uptake. CONCLUSIONS This study showed that a 51% decrease in FDG uptake during chemoradiation was a sensitive and accurate cut-point for predicting PFS. Stage T and decrease in FDG uptake were 2 independent predictive factors for 5-year PFS, CSS, and OS.
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Chang WL, Lin FC, Yen CJ, Cheng H, Lai WW, Yang HB, Sheu BS. Tumor length assessed by miniprobe endosonography can predict the survival of the advanced esophageal squamous cell carcinoma with stricture receiving concurrent chemoradiation. Dis Esophagus 2011; 24:590-5. [PMID: 21539673 DOI: 10.1111/j.1442-2050.2011.01195.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
There were tumor strictures commonly encountered in the esophageal squamous cell carcinoma (ESCC) to limit the conventional echoendoscope for exact tumor staging and size measurements. This study evaluated the role of miniprobe endosonography (EUS) to predict the survival of ESCC patients after concurrent chemoradiation therapy (CCRT). This study prospectively enrolled ESCC patients to receive high-frequency miniprobe EUS for the assessments of the tumor size and tumor-node-metastasis (TNM) stage. For the patients defined with advanced stages to receive CCRT as initial therapy, the tumor size parameters assessed by EUS were analyzed for their correlation with the treatment response and the patients' survivals. Fifty-four patients, >96% with advanced TNM stage III or IV, were enrolled with a medium follow-up of 320.5 days. Almost all of the 54 cases had partial or complete stricture of the esophageal lumens due to the tumor obstructions at enrollment. The overall median survival was 18.6 months, and the 1- and the 2-year survival rates were 64.9 and 45.2%, respectively. Patients with initial tumor length <6 cm assessed by the pre-CCRT EUS had a better survival than those with length ≥6 cm (median survival: >56.5 months vs. 11.5 months, P= 0.006). The patients with initial tumor length <6 cm had a higher rate of downstage than those with tumor length ≥6 cm after the first course of CCRT (80.0% vs. 16.7%, P= 0.035). Multivariate Cox regression confirmed the initial tumor length (hazard ratio [HR]= 1.21, P= 0.034) as well as the presence of distal metastasis are both independent predictors of the survival in ESCC patients receiving CCRT. For the ESCC patients, commonly with tumor stricture, the miniprobe EUS to assess tumor length before CCRT can predict the treatment response and the survivals.
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Affiliation(s)
- W-L Chang
- Institute of Clinical Medicine, Department of Internal Medicine National Cheng Kung University Hospital, and Medical College, National Cheng Kung University, Tainan, Taiwan
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Misra S, Choi M, Livingstone AS, Franceschi D. The role of endoscopic ultrasound in assessing tumor response and staging after neoadjuvant chemotherapy for esophageal cancer. Surg Endosc 2011; 26:518-22. [PMID: 21938577 DOI: 10.1007/s00464-011-1911-y] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2011] [Accepted: 08/06/2011] [Indexed: 02/07/2023]
Abstract
BACKGROUND Although the role of endoscopic ultrasound (EUS) in the initial staging of esophageal cancer is well established, its role in assessing tumor response and staging esophageal cancers after neoadjuvant chemotherapy (NAC) is controversial, and this study aimed to investigate this role. METHODS This study retrospectively analyzed 110 patients with esophageal cancer who underwent EUS by single surgeon before and after NAC. Tumor response was assessed before and after NAC. Patients with more than a 50% reduction in tumor size based on EUS evaluation were classified as having a significant response to chemotherapy, and those with less than a 50% reduction were categorized as having a partial response. Disease stage was established by tumor node metastasis (TNM) classification. Initial staging was performed using EUS and computed tomography (CT) scans of the chest and abdomen. The EUS-determined stage was compared with the postsurgical pathologic stage. χ(2) analysis and Fisher's exact testing were performed. RESULTS A response to NAC was shown by 96 patients (87.3%) and no response by 14 patients (12.7%). Of the 96 responding patients, 37 (38.5%) showed a significant response, whereas 43 (61.5%) of 69 patients showed a partial response. The EUS staging correlated well with the pathologic staging for 9 (64.3%) of the 14 nonresponders and for 34 (35.4%) of the 96 responders to NAC (P = 0.04). The EUS accurately predicted both the T and N status for 26 (23.6%) of the 110 patients. Prediction of N status was significantly more accurate than prediction of the T stage for the post-NAC patients. Of the 110 patients, 43 (39.1%) patients had an accurate T-stage prediction, and 64 (58.2%) had an accurate N stage match (P = 0.02). The T stage was overstaged for 60 (54.5%) of the patients and understaged for 7 of the patients (6.4%).The study found overstaging of the T stage to be more common among the patients who responded to chemotherapy. The N stage was overstaged for 25 (22.7%) and understaged for 21 (19.1%) of the 110 patients. CONCLUSION The findings showed EUS to be a useful tool for assessing response to chemotherapy and for evaluating the extent of disease, thus facilitating surgical decision making. However, EUS is an unreliable tool for staging esophageal cancer after NAC. Overstaging of the T stage is significantly more common and could be related to the inflammatory effect or fibrosis after NAC.
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Affiliation(s)
- Subhasis Misra
- DeWitt Daughtry Family Department of Surgery, Division of Surgical Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
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Tu CH, Muto M, Horimatsu T, Taku K, Yano T, Minashi K, Onozawa M, Nihei K, Ishikura S, Ohtsu A, Yoshida S. Submucosal tumor appearance is a useful endoscopic predictor of early primary-site recurrence after definitive chemoradiotherapy for esophageal squamous cell carcinoma. Dis Esophagus 2011; 24:274-8. [PMID: 21087347 DOI: 10.1111/j.1442-2050.2010.01141.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Chemoradiotherapy (CRT) for esophageal cancer is disadvantageous because of a high locoregional failure rate. Detecting early small recurrent cancers at the primary site is necessary for potential salvage treatment. However, most endoscopists are inexperienced and therefore, a role for surveillance endoscopy after complete remission (CR) has not been established. We retrospectively evaluated serial surveillance endoscopic images from patients eventually proved to have primary-site recurrence in order to identify useful endoscopic features for early diagnosis. From January 2000 to December 2004, 303 patients with esophageal squamous cell carcinoma underwent definitive CRT, and 133 of them achieved CR. The surveillance endoscopic images stored at intervals of 1-3 months for the 16 patients with recurrence only at the primary tumor site and the 61 patients with no recurrence were collected for reexamination. Among 133 patients who achieved CR, 16 (12%) developed only local recurrence at the primary site. Thirteen of the 16 primary-site recurrent tumors (81%) appeared as submucosal tumors (SMT), with the remaining appearing as erosions or mild strictures. Of biopsy-proven recurrences, 81% were preceded by newly developed lesions such as SMT, erosions, or mild strictures detected by earlier surveillance endoscopies. For all 77 patients achieving CR with no metastasis, 86% of the evolving SMT with negative biopsies were eventually confirmed as cancer at later endoscopies. Thirteen of the 21 evolving lesions were subsequently confirmed as recurrent cancer. Early primary-site recurrence of esophageal cancer after a complete response to CRT is detectable with frequent endoscopic surveillance. SMT appearance is a useful endoscopic sign of early recurrence, as well as a predictor of subsequent diagnosis of recurrence.
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Affiliation(s)
- C-H Tu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan
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Smith BR, Chang KJ, Lee JG, Nguyen NT. Staging accuracy of endoscopic ultrasound based on pathologic analysis after minimally invasive esophagectomy. Am Surg 2010; 76:1228-1231. [PMID: 21140689 DOI: 10.1177/000313481007601122] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2025]
Abstract
Endoscopic ultrasonography (EUS) is a common staging modality used in patients with esophageal cancer. The objective of this analysis was to evaluate the accuracy and sensitivity of EUS in determining the depth of penetration (T stage) and nodal status (N stage) in patients with esophageal cancer who underwent minimally invasive esophagectomy (MIE). A retrospective analysis of all patients at a university hospital who underwent preoperative EUS followed by MIE for cancer was performed. We compared the results of preoperative EUS to final pathologic analyses of the esophageal specimen, examining the accuracy of EUS staging. Ninety-five patients with esophageal cancer who underwent MIE had preoperative EUS. Twenty-four of the 95 patients were excluded for lack of a repeat EUS after neoadjuvant therapy before resection. Hence, 71 patients were evaluated for the accuracy of EUS staging. The accuracy of EUS for T0 disease was 80 per cent; T1 disease was 75 per cent; T2 disease was 39 per cent; and T3 disease was 88 per cent. The overall EUS accuracy for T stage was 72 per cent with overstaging occurring mostly for pathologic T1 tumors in 18 per cent and understaging occurring mostly for pathologic T3 tumors in 11 per cent. The sensitivity and specificity for detection of nodal involvement were 79 per cent and 74 per cent, respectively. However the accuracy for T and N staging by EUS after neoadjuvant therapy decreased to 63 per cent and 38 per cent, respectively. Endoscopic ultrasound in the absence of neoadjuvant therapy is a relatively accurate and sensitive modality for determining the depth of tumor penetration and the presence of nodal disease in patients with esophageal carcinoma. The accuracy for T and N staging is less reliable after neoadjuvant therapy.
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Affiliation(s)
- Brian R Smith
- Department of Surgery, University of California, Irvine Medical Center, Orange, California 92868, USA
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Courrech Staal EFW, Aleman BMP, Boot H, van Velthuysen MLF, van Tinteren H, van Sandick JW. Systematic review of the benefits and risks of neoadjuvant chemoradiation for oesophageal cancer. Br J Surg 2010; 97:1482-96. [DOI: 10.1002/bjs.7175] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Abstract
Background
Surgery alone for locally advanced oesophageal cancer is associated with low cure rates. The benefits and risks of neoadjuvant chemoradiation for patients with oesophageal cancer were evaluated.
Methods
A systematic review of publications between 2000 and 2008 on neoadjuvant chemoradiation for oesophageal cancer was undertaken.
Results
Thirty-eight papers comprising 3640 patients met the inclusion criteria. Chemoradiation regimens varied widely with a predominance of 5-fluorouracil/cisplatin chemotherapy. Chemoradiation-related toxicity was reported in only ten studies and consisted mainly of neutropenia. The chemoradiation-related mortality rate was 2·3 per cent. The mean R0 resection rate and pathological complete response (pCR) rate were 88·4 and 25·8 per cent respectively. Postoperative morbidity was not uniformly reported. The in-hospital mortality rate after oesophagectomy following chemoradiation was 5·2 per cent. Five-year survival rates varied from 16 to 59 per cent in all patients and from 34 to 62 per cent in those with a pCR. Chemoradiation had a temporary negative effect on quality of life.
Conclusion
Neoadjuvant chemoradiation regimens for oesophageal cancer vary widely. Besides traditional outcome variables (such as survival), other parameters should be analysed (for example toxicity) to assess whether the risks of chemoradiation are sufficiently compensated for by the benefits.
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Affiliation(s)
- E F W Courrech Staal
- Department of Surgery, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - B M P Aleman
- Department of Radiotherapy, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - H Boot
- Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - M-L F van Velthuysen
- Department of Pathology, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - H van Tinteren
- Department of Biometrics, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
| | - J W van Sandick
- Department of Surgery, The Netherlands Cancer Institute–Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Diaz R, Reynes G, Tormo A, de Juan M, Gironés R, Segura Á, Aparicio J, Richart P, de la Cueva H, García J. Long-term results of neoadjuvant chemotherapy and combined chemoradiotherapy before surgery in the management of locally advanced oesophageal cancer: a single-centre experience. Clin Transl Oncol 2009; 11:835-41. [DOI: 10.1007/s12094-009-0452-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
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Kalaitzakis E, Meenan J. Controversies in the use of endoscopic ultrasound in esophageal cancer staging. Scand J Gastroenterol 2009; 44:133-44. [PMID: 18654933 DOI: 10.1080/00365520802273066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Evangelos Kalaitzakis
- Department of Gastroenterology, St Thomas' Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
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Leblanc J, Kongkam P. Endoscopic Ultrasound-Guided Fine Needle Aspiration (EUS-FNA) Diagnosis of Recurrent Anal Cancer After Chemoradiation and Negative Forceps Biopsies: A Case Report. Clin Med Oncol 2009; 3:59-62. [PMID: 20689610 PMCID: PMC2872600 DOI: 10.4137/cmo.s993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
A 69-year-old woman with a history of uT2 N0 post-treated anal squamous cell cancer (SCC) presented for EUS for perianal pain. Two months prior, a digital rectal examination was significant for an indurated lesion on the left lateral rectal wall just proximal to the dentate line. A sigmoidoscopy revealed mild narrowing of the anal canal and an ulcerated friable mucosa in the same area. A biopsy demonstrated ulceration without malignancy. EUS showed a hypoechoic, non-circumferential, left-sided distal rectal mass. EUS-FNA was performed. Cytology demonstrated poorly differentiated SCC. This was confirmed by subsequent surgical resection. While endoscopic biopsy of suspected anal recurrences is usually sufficient, histologic or cytologic confirmation are necessary, as radiation-induced changes are difficult to differentiate from tumor recurrence. This case demonstrates that EUS-FNA is useful in surveillance of anal SCC when there is a high clinical suspicion of recurrence.
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Affiliation(s)
- Julia Leblanc
- Indiana University Medical Center, Division of Gastroenterology and Hepatology
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Abstract
Esophageal cancer is the third most common malignancy of the alimentary tract. The incidence of esophageal cancer has steadily increased over the past three decades. Almost all therapeutic modalities for esophageal cancer are associated with a considerable mortality and morbidity. Consequently, there has been growing concern regarding effective management of esophageal cancer. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is playing an increasing role in the management of esophageal cancer, offering potential advantages in the accuracy of disease assessment at a number of decision points in the management pathway. This review evaluates the critical role of FDG-PET in (i) diagnosis, (ii) preoperative staging, (iii) monitoring of response to neoadjuvant therapy, (iv) assessment of recurrence and (v) prediction of prognosis of esophageal cancer. We have also compared diagnostic performance of FDG-PET and other current technologies such as computed tomography scan and endoscopic ultrasonography based on available evidence.
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Response Evaluation by Endoscopy, Rebiopsy, and Endoscopic Ultrasound Does Not Accurately Predict Histopathologic Regression After Neoadjuvant Chemoradiation for Esophageal Cancer. Ann Surg 2008; 248:902-8. [DOI: 10.1097/sla.0b013e31818f3afb] [Citation(s) in RCA: 131] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Prospective comparison of the perceived preoperative computed tomographic, endosonographic and histopathological stage of oesophageal cancer related to body mass indices. Eur Radiol 2008; 19:935-40. [DOI: 10.1007/s00330-008-1208-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2008] [Revised: 07/29/2008] [Accepted: 08/24/2008] [Indexed: 01/01/2023]
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Abstract
PURPOSE OF REVIEW Esophageal cancer staging continues to evolve, especially for advanced cases. Computer tomography (CT) scan of the thorax and abdomen to detect metastatic disease, and endoscopic ultrasound with fine needle aspiration (EUS-FNA) remain the preferred methods. Several recent studies have evaluated alternative methods for locoregional and distant disease detection and staging. RECENT FINDINGS There seems to be emerging roles for fluorine-18 fluorodeoxyglucose (FDG)-PET, laparoscopic staging, and high-resolution T2-weighted MRI in esophageal cancer staging. Perfusion CT and FDG-PET and FDG-PET/CT may have an emerging role in assessing response to neoadjuvant therapy. Restaging following neoadjuvant therapy remains suboptimal. A 50% or more reduction of tumor thickness by EUS postchemotherapy continues to be the best measure for tumor downstaging survival, while FDG-PET/CT may be more accurate than EUS-FNA and CT scan for predicting nodal status and complete responders after neoadjuvant therapy. Potential methylation analysis, digital image analysis, and fluorescence in-situ hybridization on EUS-FNA samples may increase the yield and prove to be better than routine cytology. SUMMARY For advanced esophageal cancer, locoregional staging is best performed with EUS-FNA, with CT scan of the thorax and abdomen and FDG-PET, to detect metastatic disease. The role of EUS in restaging following neoadjuvant therapy remains controversial, with recent studies showing that FDG-PET/CT may be more accurate than EUS-FNA and CT scan for predicting nodal status and complete responders after neoadjuvant therapy.
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Abstract
Upper gastrointestinal tumors involving the esophagus and the stomach are a serious public health problem worldwide. The West has seen a dramatic increase in the incidence of gastroesophageal cancers in the past 2 decades. Although Barrett esophagus has been well characterized, the exact pathway to developing frank malignancy remains undefined. Current treatments for locoregional disease include surgery, chemotherapy, radiation therapy, or some combination thereof. Clinical trials are currently investigating biologic agents that target signaling pathways in carcinogenesis. Whether this research translates into an improved therapeutic index remains to be seen. This review provides a comprehensive update to physicians and residents who contribute to the care of these patients. Studies in the English language were identified searching PubMed (January 1, 1980, through February 29, 2008) using the terms esophagus, gastric, carcinoma, adenocarcinoma, squamous cell, radiation, chemotherapy, surgery, esophagectomy, and targeted therapy.
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Affiliation(s)
- Nikhil Khushalani
- Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
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Higuchi I, Yasuda T, Yano M, Doki Y, Miyata H, Tatsumi M, Fukunaga H, Takiguchi S, Fujiwara Y, Hatazawa J, Monden M. Lack of fludeoxyglucose F 18 uptake in posttreatment positron emission tomography as a significant predictor of survival after subsequent surgery in multimodality treatment for patients with locally advanced esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 2008; 136:205-12, 212.e1-3. [PMID: 18603077 DOI: 10.1016/j.jtcvs.2008.02.016] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2007] [Revised: 01/25/2008] [Accepted: 02/15/2008] [Indexed: 01/24/2023]
Abstract
OBJECTIVE Patients with advanced esophageal squamous cell carcinoma receive neoadjuvant chemotherapy or chemoradiotherapy to improve survival, but benefits are observed only in those with histologic response. Positron emission tomography with fludeoxyglucose F 18 (INN fludeoxyglucose [(18)F]) detects accumulation of glucose analog in viable cancer cells. This study investigated the usefulness of positron emission tomography with fludeoxyglucose F 18 in assessment of response of advanced esophageal squamous cell carcinoma to neoadjuvant treatment to establish new criteria to predict postoperative long-term survival. METHODS Fifty patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant therapy (chemotherapy 35, chemoradiotherapy 15) underwent positron emission tomography with fludeoxyglucose F 18 before surgical resection in evaluation of posttreatment maximum standardized uptake value, residual tumor size (maximum square area of longitudinal axis), histologic response, and postoperative survival. RESULTS After treatment, uptake was not noted in 21 patients (posttreatment maximum standardized uptake value < 2.5, negative) but was detected in 29 (> or = 2.5, positive). Residual tumor size ranged from 0 to 54.0 mm(2) for negative results and 55.0 to 676.0 mm(2) for positive, clearly distinguishing histologic major response from nonresponse. The negative group demonstrated significantly higher 5-year cause-specific survival (67.7%) and lower hematogenous recurrence (4.8%) than the 36.5% and 37.0% values in the positive group, (P < .0042 and P = .0083, respectively). Univariate Cox regression analyses identified posttreatment maximum standardized uptake value (cutoff 2.5) as the only preoperative prognostic factor (P = .0071). CONCLUSION Posttreatment positron emission tomography with fludeoxyglucose F 18 reliably predicted histologic response and postoperative survival in advanced esophageal squamous cell carcinoma. This tool could potentially be used to tailor optimal treatment according to individual responses.
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Affiliation(s)
- Ichirou Higuchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
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Mesenas S, Vu C, McStay M, Forshaw M, Doig L, Mason R, Boyle N, Meenan J. A large series, resection controlled study to assess the value of radial EUS in restaging gastroesophageal cancer following neoadjuvant chemotherapy. Dis Esophagus 2008; 21:37-42. [PMID: 18197937 DOI: 10.1111/j.1442-2050.2007.00731.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The true value of endoscopic ultrasound (EUS) post-neoadjuvant chemotherapy for esophageal carcinoma is not established. Superior loco-regional detail may yield useful staging and prognostic information but information on its accuracy, as compared with computed tomography (CT), remains undefined and limited by small study size. We prospectively studied 109 patients with gastroesophageal cancer; 99 of whom were undergoing surgery. All had EUS and helical CT imaging before and after neoadjuvant chemotherapy and the results were compared with pathological staging of resected specimens. Tumor response was assessed by the reduction in maximal tumor depth at EUS and correlated with patient survival. There was no difference in T and N stage accuracies between EUS and CT following neoadjuvant chemotherapy. manova showed a reduction in maximal tumor depth by > 50% at EUS to be associated with longer survival (relative risk = 0.48, P < 0.05). EUS responders had a median survival of 38 months compared to 30 months for non-responders (P < 0.05). The identification of lymphadenopathy at radial EUS was not predictive of survival. This large series study demonstrates the staging accuracy of CT and non-biopsy EUS in the setting of neoadjuvant chemotherapy for gastroesophageal cancer to be equivalent and poor. An endosonography may contribute useful clinical information in respect of potential survival. It is questionable whether radial EUS should be included in protocols for restaging.
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Affiliation(s)
- S Mesenas
- Department of Gastroenterology and Upper Gastro-intestinal Surgery, Guy's and St Thomas' Hospital, London, UK
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49
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Abstract
The divergence in epidemiology between the East and West has made interpretation of data in the literature more difficult and has affected the choice of the most appropriate surgical technique and treatment strategies. The management of esophageal cancer certainly has evolved, and many more options are available. Stage-directed strategies and individualization of treatment are important considerations. Surgeons play a central role in directing management of this disease by advising how best to integrate surgical therapy with nonoperative programs. Surgeons should aim at improving their results further, so that the best results of surgery are compared with seemingly "safer" nonsurgical therapies. Low death rates have been achieved in specialized centers, but there still is much room for improvement in morbidity rates. Even with the best surgical resection and chemoradiation therapy, distant failure remains a barrier to improved survival rates. Therapeutic improvements will require more effective systemic drugs and a better ability to predict responders with precision. Management strategies will evolve further, with improvements in molecular techniques, imaging methods, and introduction of more novel tumoricidal agents. The challenge for the future is to test strategies critically in a scientific, unbiased manner and to explore other innovative treatments.
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Affiliation(s)
- Simon Law
- Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China.
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Nam TK, Lee JH, Cho SH, Chung IJ, Ahn SJ, Song JY, Yoon MS, Chung WK, Nah BS. Low hMLH1 expression prior to definitive chemoradiotherapy predicts poor prognosis in esophageal squamous cell carcinoma. Cancer Lett 2007; 260:109-17. [PMID: 18053639 DOI: 10.1016/j.canlet.2007.10.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2007] [Revised: 10/18/2007] [Accepted: 10/18/2007] [Indexed: 12/31/2022]
Abstract
The present study evaluated the pretreatment expression patterns of hMLH1, MDM2, p53, and pRb protein to determine whether these could predict the outcome of definitive concurrent chemoradiotherapy (CCRT) in 51 patients with stage I-IVa esophageal squamous cell carcinoma. High immunoreactivies of hMLH1, MDM2, p53, and pRb were detected in 90.2%, 19.6%, 27.5%, and 66.7% of entire patients, respectively. High hMLH1 expression was found to favor earlier stage, less locoregional failure, and longer cause-specific survival, and all were with significance. However, the expressions of MDM2, p53, and pRb were not found to be clinically significant. Thirty-three patients with high hMLH1 and pRb expression tended to survive longer than four patients with low hMLH1 and pRb expression. We suggest that the expression of hMLH1 is a potential marker of tumor response and survival. Determinations of this protein expression might be useful for selecting esophageal squamous cell carcinoma patients for definitive CCRT.
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Affiliation(s)
- Taek-Keun Nam
- Department of Radiation Oncology, Chonnam National University Medical School, Gwangju, Republic of Korea.
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