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Xu M, Zhang Y, Zhao K, Jiang H, Wang G, Wu Y, Wang Y, Liu N, Su X. Prediction of pathological response to neoadjuvant immunochemotherapy with baseline and post-treatment 18F-FDG PET imaging biomarkers in patients with locally advanced gastric cancer. BMC Cancer 2025; 25:378. [PMID: 40022087 PMCID: PMC11871599 DOI: 10.1186/s12885-025-13765-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 02/18/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Neoadjuvant immunochemotherapy (NICT) has shown promising therapeutic benefits in patients with locally advanced gastric cancer (LAGC). Our study aimed to predict the pathological response to NICT in LAGC before surgery by correlating the metabolic parameters of baseline and post-treatment 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) of the primary lesion with the pathological response following radical surgery. METHODS Thirty-six LAGC patients who received three cycles of NICT (combination of sintilimab and CapeOx), followed by radical surgery, were included in this study. Both baseline 18F-FDG PET/CT (bPET) and post-treatment 18F-FDG PET/CT (pPET) were conducted, the metabolic parameters derived from the PET/CT scans, including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on bPET and pPET (bSUVmax and pSUVmax, bMTV and pMTV, bTLG and pTLG), as well as their reductions post-treatment (ΔSUVmax, ΔMTV, and ΔTLG), were assessed for their correlation with treatment efficacy and tumor regression grade (TRG) following NICT. RESULTS Out of the 36 patients, 13 patients had a good response (GR), which included 5 cases with TRG 0 and 8 cases with TRG 1. Conversely, 23 patients exhibited a poor response (PR), with 20 patients having TRG 2 and 3 patients having TRG 3. Univariate analysis revealed that pMTV and pTLG in the GR group were significantly lower compared to the PR group (all p < 0.05). The identified cutoff values of pMTV and pTLG were 1.68 cm³ (area under the cure (AUC) = 0.683) and 4.71 cm³ (AUC = 0.683) for the GR and PR groups, respectively. On receiver operating characteristic (ROC) curve analyses, these values corresponded to sensitivity, specificity, and accuracy of 68.8%, 80.0%, and 73.1%, respectively, with no statistically significant differences between them after the DeLong test and McNemar test (all p > 0.05). Furthermore, bSUVmax, bMTV, bTLG, ΔSUVmax, ΔMTV, and ΔTLG in the TRG 0 group were significantly higher than those in the TRG 1 group (all p < 0.05). Upon performing ROC curve analyses for the TRG 0 group, the thresholds for bSUVmax, bMTV, bTLG, ΔSUVmax, ΔMTV, and ΔTLG were determined to be 7.8 (AUC = 0.916), 36.76 (AUC = 0.768), 105.55 (AUC = 0.819), 4.82 (AUC = 0.923), 22.64 (AUC = 0.807), and 104.7 (AUC = 0.845), with no statistically significant differences between them after the DeLong test (all p > 0.05). These thresholds demonstrated high sensitivity (80% for bMTV and 100% for others), specificity (83.9%, 71.0%, 67.7%, 83.9%, 61.3%, and 71.0%), and accuracy (86.1%, 66.7%, 72.2%, 86.1%, 66.7%, and 75.0%) in predicting TRG 0 after NICT, with no statistically significant differences between them after the McNemar test (all p > 0.05). CONCLUSIONS Imaging biomarkers from the combination of baseline and post-treatment 18F-FDG PET/CT showed potential in predicting pathological response to NICT in LAGC patients before surgery.
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Affiliation(s)
- Mimi Xu
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yafei Zhang
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Kui Zhao
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Haiping Jiang
- Oncology Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Guangfa Wang
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yan Wu
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China
| | - Yu Wang
- The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310005, China
| | - Nian Liu
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
| | - Xinhui Su
- Department of Nuclear Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
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Meng F, Yang Y, Wang X, Cai F, Liang H, Zhang R, Deng J. Imaging lymph node regression can predict the pathological tumor regression grade in gastric cancer after neoadjuvant treatment. Surgery 2023; 174:836-843. [PMID: 37562986 DOI: 10.1016/j.surg.2023.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 05/24/2023] [Accepted: 07/08/2023] [Indexed: 08/12/2023]
Abstract
BACKGROUND Neoadjuvant chemotherapy has become the standard treatment for locally advanced gastric cancer. The tumor regression grade system is an effective and widely used tool for the evaluation of treatment response to neoadjuvant chemotherapy. However, whether tumor regression grade could be predicted using clinical characteristics is uncertain. METHODS A total of 287 locally advanced gastric cancer patients from 2014 to 2021 were retrospectively included. According to the College of American Pathologists' tumor regression grade system, patients were classified into response group (tumor regression grade 0-1) and non-response group (tumor regression grade 2-3). Associations between clinical characteristics and neoadjuvant chemotherapy response were performed by the logistic regression model. The Kaplan-Meier method was used to estimate the survival. A prediction scoring system was constructed based on the β coefficients of multivariate analysis. The receiver operating characteristic curve and decision curve analysis were used to evaluate the performance of the predictive scoring system. RESULTS Survival analysis showed that patients with tumor regression grades 0 to 1 had significantly better disease-free survival and overall survival than the tumor regression grades 2 to 3. Tumor differentiation, ycT stage, immunotherapy, and lymph node regression were independent predictors of pathological response to neoadjuvant chemotherapy. We further developed a scoring system to predict the tumor regression grade. The receiver operating characteristic and decision curve analysis showed good predictive performance of the scoring system. CONCLUSION Lymph node regression could be used as a predictor for pathological response. We developed a scoring system to predict the treatment response of patients with gastric cancer receiving neoadjuvant chemotherapy. The scoring system based on the predictors could provide guidance for making clinical decisions.
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Affiliation(s)
- Feiyu Meng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, P. R. China
| | - Yang Yang
- Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China
| | - Xinyu Wang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, P. R. China
| | - Fenglin Cai
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, P. R. China
| | - Han Liang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, P. R. China
| | - Rupeng Zhang
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, P. R. China
| | - Jingyu Deng
- Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, P. R. China.
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Enhanced CT-based radiomics predicts pathological complete response after neoadjuvant chemotherapy for advanced adenocarcinoma of the esophagogastric junction: a two-center study. Insights Imaging 2022; 13:134. [PMID: 35976518 PMCID: PMC9385906 DOI: 10.1186/s13244-022-01273-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Accepted: 07/20/2022] [Indexed: 01/19/2023] Open
Abstract
Purpose This study aimed to develop and validate CT-based models to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for advanced adenocarcinoma of the esophagogastric junction (AEG). Methods Pre-NAC clinical and imaging data of AEG patients who underwent surgical resection after preoperative-NAC at two centers were retrospectively collected from November 2014 to September 2020. The dataset included training (n = 60) and external validation groups (n = 32). Three models, including CT-based radiomics, clinical and radiomics–clinical combined models, were established to differentiate pCR (tumor regression grade (TRG) = grade 0) and nonpCR (TRG = grade 1–3) patients. For the radiomics model, tumor-region-based radiomics features in the arterial and venous phases were extracted and selected. The naïve Bayes classifier was used to establish arterial- and venous-phase radiomics models. The selected candidate clinical factors were used to establish a clinical model, which was further incorporated into the radiomics–clinical combined model. ROC analysis, calibration and decision curves were used to assess the model performance. Results For the radiomics model, the AUC values obtained using the venous data were higher than those obtained using the arterial data (training: 0.751 vs. 0.736; validation: 0.768 vs. 0.750). Borrmann typing, tumor thickness and degree of differentiation were utilized to establish the clinical model (AUC-training: 0.753; AUC-validation: 0.848). The combination of arterial- and venous-phase radiomics and clinical factors further improved the discriminatory performance of the model (AUC-training: 0.838; AUC-validation: 0.902). The decision curve reflects the higher net benefit of the combined model. Conclusion The combination of CT imaging and clinical factors pre-NAC for advanced AEG could help stratify potential responsiveness to NAC. Supplementary Information The online version contains supplementary material available at 10.1186/s13244-022-01273-w.
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Koppula BR, Fine GC, Salem AE, Covington MF, Wiggins RH, Hoffman JM, Morton KA. PET-CT in Clinical Adult Oncology: III. Gastrointestinal Malignancies. Cancers (Basel) 2022; 14:cancers14112668. [PMID: 35681647 PMCID: PMC9179927 DOI: 10.3390/cancers14112668] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/20/2022] [Accepted: 05/20/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Positron emission tomography (PET), typically combined with computed tomography (CT), has become a critical advanced imaging technique in oncology. With PET-CT, a radioactive molecule (radiotracer) is injected in the bloodstream and localizes to sites of tumor because of specific cellular features of the tumor that accumulate the targeting radiotracer. The CT scan, performed at the same time, provides information to facilitate the characterization of radioactivity from deep or dense structures, and to provide detailed anatomic information. PET-CT has a variety of applications in oncology, including staging, therapeutic response assessment, restaging and surveillance. This series of six review articles provides an overview of the value, applications, and imaging interpretive strategies of PET-CT in the more common adult malignancies. The third report in this series provides a review of PET-CT imaging in gastrointestinal malignancies. Abstract PET-CT is an advanced imaging modality with many oncologic applications, including staging, assessment of response to therapy, restaging and longitudinal surveillance for recurrence. The goal of this series of six review articles is to provide practical information to providers and imaging professionals regarding the best use of PET-CT for specific oncologic indications, and the potential pitfalls and nuances that characterize these applications. In the third of these review articles, key tumor-specific clinical information and representative PET-CT images are provided to outline the role that PET-CT plays in the management of patients with gastrointestinal malignancies. The focus is on the use of 18F fluorodeoxyglucose (FDG), rather than on research radiopharmaceuticals under development. Many different types of gastrointestinal tumors exist, both pediatric and adult. A discussion of the role of FDG PET-CT for all of these is beyond the scope of this review. Rather, this article focuses on the most common adult gastrointestinal malignancies that may be encountered in clinical practice. The information provided here will provide information outlining the appropriate role of PET-CT in the clinical management of patients with gastrointestinal malignancies for healthcare professionals caring for adult cancer patients. It also addresses the nuances and provides interpretive guidance related to PET-CT for imaging providers, including radiologists, nuclear medicine physicians and their trainees.
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Affiliation(s)
- Bhasker R. Koppula
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
| | - Gabriel C. Fine
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
| | - Ahmed Ebada Salem
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
- Department of Radio Diagnosis and Intervention, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt
| | - Matthew F. Covington
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
| | - Richard H. Wiggins
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
| | - John M. Hoffman
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
| | - Kathryn A. Morton
- Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84132, USA; (B.R.K.); (G.C.F.); (A.E.S.); (M.F.C.); (R.H.W.); (J.M.H.)
- Summit Physician Specialists, Intermountain Healthcare Hospitals, Murray, UT 84123, USA
- Correspondence: ; Tel.: +1-801-581-7553
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Predicting pathological response and overall survival in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy: the role of PET/computed tomography. Nucl Med Commun 2022; 43:560-567. [PMID: 35045553 DOI: 10.1097/mnm.0000000000001534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Gastric cancer is the second leading cause of cancer-related deaths, with a 5-year survival rate of about 20-25%. The ability to predict pathological response (PR) to neoadjuvant chemotherapy (NACT); hence, overall survival (OS) probability of patients can allow the clinician to individualize treatment strategies. We investigated the role of F-18 fluorodeoxyglucose PET-computed tomography (F-18 FDG PET/CT) in predicting histopathologic response and prognosis in locally advanced gastric cancer (LAGC) patients undergoing NACT. METHODS F-18FDG PET/CT images taken before and after NACT, adenocarcinoma histopathology and operation pyesis reports of 43 LAGC patients were analyzed. Maximum (SUVmax) and mean (SUVmean) standardized uptake values, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of lesions were measured before and after NACT. Changes in percentage were calculated for ΔSUVmax%, ΔSUVmean%, ΔMTV%, ΔTLG%, and cutoff values were determined by receiver operating characteristic curve analysis. NACT response in pathology pyesis was determined according to the College of American Pathologists classification. PR and OS were analyzed with Kaplan-Meier and Cox proportional hazards regression models based on cutoffs found with PET measurements. RESULTS Cutoffs were ΔSUVmax = 33.31%, ΔSUVmean = 42.96%, ΔMTV = 30.38%, and ΔTLG = 28.14%, and all patients showed significance in PR and OS based on these cutoffs (all P < 0.01). PET/CT findings before and after NACT (ΔMTV > 30.38%, ΔTLG > 28.14%) predicted PR with 100% sensitivity and specificity. Multivariate analysis showed ΔSUVmean as an independent risk factor predicting OS (hazard ratio 0.348, 95% confidence interval 2.91-22.3, P = 0.03). CONCLUSIONS Metabolic parameters obtained with F-18 FDG PET/CT scanning before and after NACT in LAGC patients can accurately predict PR and OS.
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Shoji Y, Nunobe S, Nishie N, Yagi S, Makuuchi R, Ida S, Kumagai K, Ohashi M, Ishiyama A, Yoshio T, Hirasawa T, Fujisaki J, Sano T. Impact of preoperative endoscopy for predicting treatment response and prognosis in patients with gastric cancer after neoadjuvant chemotherapy. Endosc Int Open 2022; 10:E62-E73. [PMID: 35047336 PMCID: PMC8759937 DOI: 10.1055/a-1635-5855] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/27/2021] [Indexed: 11/12/2022] Open
Abstract
Background and study aims Response evaluation criteria in solid tumors (RECIST) have been the gold standard to preoperatively predict treatment response and prognosis in patients with gastric cancer (GC) after neoadjuvant chemotherapy (NAC); however, methods for patients without evaluable lesions by RECIST are not yet confirmed. The aim of this study was to assess the utility of preoperative endoscopy for predicting treatment response and prognosis in patients with GC after NAC. Patients and methods This retrospective study included 105 patients with initially resectable GC who underwent NAC followed by surgical treatment. Preoperative factors for predicting treatment response and survival outcomes were analyzed. Results The number of patients classified as responders using preoperative endoscopic assessment, RECIST, and postoperative pathological evaluation were 25 (23.8 %), 28 (26.7 %), and 18 (17.1 %), respectively. Forty-three patients (41 %) were classified as non-targeted disease only, and their treatment responses were not evaluable by RECIST. Multivariate analysis identified endoscopic response as an independent preoperative factor to predict postoperative histological treatment response (odds ratio = 4.556, 95 % CI = 1.169-17.746, P = 0.029). Endoscopic treatment response was the only independent preoperative predictive factor for overall survival (OS) (hazard ratio = 0.419, 95 % confidence interval (CI) = 0.206-0.849, P = 0.016). Further, endoscopic treatment response was available for 33 patients (76.7 %) with non-targeted disease only, which showed significantly different OS between endoscopic responders (80.0 %) and non-responders (43.5 %) ( P = 0.025). Conclusions Endoscopic evaluation was an independent preoperative factor to predict treatment response and prognosis in patients with GC after NAC. Endoscopic assessment may be especially valuable for patients who could not be assessed by RECIST.
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Affiliation(s)
- Yoshiaki Shoji
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Nishie
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shusuke Yagi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Rie Makuuchi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Ida
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Koshi Kumagai
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Ohashi
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akiyoshi Ishiyama
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiyuki Yoshio
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiaki Hirasawa
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Junko Fujisaki
- Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
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Wang ZL, Li YL, Li XT, Tang L, Li ZY, Sun YS. Role of CT in the prediction of pathological complete response in gastric cancer after neoadjuvant chemotherapy. Abdom Radiol (NY) 2021; 46:3011-3018. [PMID: 33566165 DOI: 10.1007/s00261-021-02967-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 01/14/2021] [Accepted: 01/16/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To explore which computed tomography (CT) features can predict pathological complete response (pCR) (ypT0N0) after neoadjuvant chemotherapy (NAC) in patients with gastric adenocarcinoma (GC). MATERIALS AND METHODS This study reviewed an institutional database of patients who underwent resection of GC after NAC and identified patients with pCR from January 2010 to December 2013. The correlations between pre-chemotherapy and post-chemotherapy CT features and pCR were analyzed. RESULTS Eleven of 199 patients with GC who achieved ypT0N0 status after NAC were classified as the pCR group in this study. After matching pCR (n = 11) and non-pCR patients (n = 44) in the ratio of 1:4, a total of 55 cases were analyzed. The binary logistic regression analysis showed that the post-chemotherapy short diameter of the largest lymph node and tumor thickness ratio reduction were independent predictors of pCR, with an area under the curve (AUC) of 0.94 on the receiver operating characteristic (ROC) curve analysis. CONCLUSION Two CT features, including the short diameter of the largest lymph node post-chemotherapy and tumor thickness ratio reduction, are good predictors of pCR after NAC in patients with GC.
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Affiliation(s)
- Zhi-Long Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China
| | - Yan-Ling Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China
| | - Xiao-Ting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China
| | - Lei Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China
| | - Zi-Yu Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China
| | - Ying-Shi Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Radiology, Peking University Cancer Hospital & Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China.
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Sun J, Wang X, Zhang Z, Zeng Z, Ouyang S, Kang W. The Sensitivity Prediction of Neoadjuvant Chemotherapy for Gastric Cancer. Front Oncol 2021; 11:641304. [PMID: 33937042 PMCID: PMC8085495 DOI: 10.3389/fonc.2021.641304] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 03/22/2021] [Indexed: 12/24/2022] Open
Abstract
The overall efficacy of neoadjuvant chemoradiotherapy (NACT) for locally advanced gastric cancer (LAGC) has been recognized. However, the response rate of NACT is limited due to tumor heterogeneity. For patients who are resistant to NACT, not only the operation timing will be postponed, patients will also suffer from the side effects of it. Thus, it is important to develop a comprehensive strategy and screen out patients who may be sensitive to NACT. This article summarizes the related research progress on the sensitivity prediction of NACT for GC in the following aspects: microRNAs, metabolic enzymes, exosomes, other biomarkers; inflammatory indicators, and imageological assessments. The results showed that there were many studies on biomarkers, but no unified conclusion has been drawn. The inflammatory indicators are related to the survival and prognosis of patients under NACT. For imageological assessments such as CT, MRI, and PET, with careful integration and optimization, they will have unique advantages in early screening for patients who are sensitive to NACT.
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Affiliation(s)
- Juan Sun
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College Hospital (CAMS), Beijing, China
| | - Xianze Wang
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College Hospital (CAMS), Beijing, China
| | - Zimu Zhang
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College Hospital (CAMS), Beijing, China
| | - Ziyang Zeng
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College Hospital (CAMS), Beijing, China
| | - Siwen Ouyang
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Peking Union Medical College Hospital (CAMS), Beijing, China
| | - Weiming Kang
- Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of General Surgery, Peking Union Medical College Hospital (CAMS), Beijing, China
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Mi L, Zhao Y, Zhao X, Yin F, Yin X, Li N, Shi J, Han X, Duan X, Zhao M, Han G, Wang J. 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Metabolic Parameters Before and After Neoadjuvant Chemotherapy Can Predict the Postoperative Prognosis of Locally Advanced Gastric Cancer. Cancer Biother Radiopharm 2020; 36:662-671. [PMID: 32783634 DOI: 10.1089/cbr.2020.3942] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Objective: To explore the value of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) metabolic parameters before and after neoadjuvant chemotherapy in predicting histopathological response and prognosis of locally advanced gastric cancer. Materials and Methods: A total of 56 patients with locally advanced gastric cancer underwent 18F-FDG PET/CT before and after neoadjuvant chemotherapy. The maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the lesions were measured before and after neoadjuvant chemotherapy. The percentage changes in the maximum standardized uptake value (ΔSUVmax%), mean standardized uptake value (ΔSUVmean%), metabolic tumor volume (ΔMTV%), and total lesion glycolysis (ΔTLG%), which were derived from 18F-FDG PET/CT, were calculated, and the cutoff values were determined by receiver operating characteristic curve analysis. Differences in progression-free survival (PFS) and overall survival (OS) between groups dichotomized by these cutoffs were analyzed using the Kaplan-Meier method and Cox proportional hazards regression model. Results: The patients were divided into histopathological responders and nonresponders according to the following cutoff values: 58.8% SUVmax reduction, 45.8% SUVmean reduction, 36.9% MTV reduction, and 57.8% TLG reduction. The differences in PFS and OS between groups dichotomized by these cutoffs were significant (all p < 0.01). Multivariate analysis suggested that a ΔTLG% > 57.8% was an independent postoperative risk factor for PFS (hazard ratio [HR] 0.348, 95% confidence interval [CI] 0.131-0.926, p = 0.035) and OS (HR 0.107, 95% CI 0.023-0.498, p = 0.004). Conclusions: The metabolic parameters before and after neoadjuvant chemotherapy of 18F-FDG PET/CT accurately reflected the chemotherapy effect, and ΔTLG% was the only independent postoperative predictive factor of PFS and OS for locally advanced gastric cancer.
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Affiliation(s)
- Lili Mi
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yan Zhao
- Department of Oncology, and The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xinming Zhao
- Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Fei Yin
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaolei Yin
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ning Li
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jianfei Shi
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xin Han
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xiaoling Duan
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Man Zhao
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Guangjie Han
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jinfeng Wang
- Department of Gastroenterology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Limited Usefulness of 18F-FDG PET/CT in Predicting Tumor Regression After Preoperative Chemotherapy for Noncardia Gastric Cancer: The Italian Research Group for Gastric Cancer (GIRCG) Experience. Clin Nucl Med 2020; 45:177-181. [PMID: 31977470 DOI: 10.1097/rlu.0000000000002911] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The present study aimed to better define the usefulness of F-FDG PET/CT in predicting pathological tumor response (PTR) and survival in patients with noncardia gastric cancer treated with preoperative chemotherapy. METHODS Seventy-one patients were recruited in 6 Italian centers. The SUV of F-FDG PET/CT was measured at baseline and after treatment, and the difference (dSUV) was computed. The association between PET indexes and PTR, assessed by the Becker score, was evaluated by nonparametric regression. The discriminant power of PET indexes with respect to the absence of PTR (Becker 2/3) was studied by receiver operating characteristic (ROC) curve and synthesized by the area under the curve (ROC-AUC). RESULTS dSUV allowed to partially discriminate between absence/presence of PTR, when expressed as either absolute value (ROC-AUC, 0.73; 95% confidence interval, 0.59-0.87) or percentage (ROC-AUC, 0.74; 95% confidence interval, 0.59-0.89). However, only extreme values of percent dSUV were really informative. All 7 patients whose F-FDG uptake had increased despite preoperative treatment showed no tumor regression at pathologic examination. Seven of the 10 patients whose metabolic response had been 70% or greater had complete or nearly complete pathologic tumor regression (Becker score 1a or 1b). The metabolic response of the remaining 54 patients, which ranged between 0% and 70%, did not permit to reliably forecast pathologic tumor regression. Survival significantly decreased with increasing Becker score but was unaffected by metabolic response. CONCLUSIONS The present study suggests that F-FDG PET/CT has limited usefulness in predicting cancer regression. The lack of metabolic response in serial measurements indicates the probable ineffectiveness of preoperative treatment.
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11
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Fu J, Tang L, Li ZY, Li XT, Zhu HF, Sun YS, Ji JF. Diffusion kurtosis imaging in the prediction of poor responses of locally advanced gastric cancer to neoadjuvant chemotherapy. Eur J Radiol 2020; 128:108974. [PMID: 32416553 DOI: 10.1016/j.ejrad.2020.108974] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 02/15/2020] [Accepted: 03/19/2020] [Indexed: 12/11/2022]
Abstract
PURPOSE To assess the efficacy of diffusion kurtosis imaging (DKI) in the prediction of the treatment response to neoadjuvant chemotherapy in patients with locally advanced gastric cancer (LAGC). METHODS A total of 31 LAGC patients were enrolled in this prospective study. All patients underwent diffusion-weighted MRI examination (with b = 01, 2001, 5001, 8002, 10004, 15004, 20006 s/mm2, the subscript denotes the number of signal averages) before and after chemotherapy. DKI and mono-exponential (b = 0, 800 s/mm2) models were built. Apparent diffusion coefficient (ADC), mean diffusivity (MD) and mean kurtosis (MK) of the LAGC tumors were measured. The absolute change values (ΔX) and percentage change values (%ΔX) of the above parameters post neoadjuvant chemotherapy (NACT) were calculated. The response was evaluated according to the pathological tumor regression grade scores (effective response group: TRG 0-2, poor response group: TRG 3). Mann-Whitney U test and receiver operating characteristic (ROC) curves were applicated for statistical analysis. RESULTS There were 17 patients in the effective response group (ERG), and 14 patients in the poor response group (PRG). The MKpre and MKpost values in PRG were significantly higher than those in ERG [(0.671 ± 0.026) and (0.641 ± 0.019) vs. (0.584 ± 0.023) and (0.519 ± 0.018), p < 0.001]. ADCpost and MDpost in PRG were significantly lower than those in ERG (p = 0.005, p =0.001). Significant differences were also observed for % ΔMK, ΔMD and ΔMK between the two groups (p < 0.05). The area under the curve (AUC) for the prediction of PRG was highest for MKpost (AUC = 0.958, cutoff value = 0.614). The MKpre and MKpost had the highest sensitivity (91.70 %) and specificity (93.80 %) in the prediction of PRG, respectively. CONCLUSION Both DKI and ADC values show potential for the prediction of the PRG in LAGC patients. The DKI parameters, especially MKpost displayed the best performance.
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Affiliation(s)
- Jia Fu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Radiology Department, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China; Department of Radiology, Civil Aviation General Hospital, No. 1 Gaojingjia, Chaoyang Road, Chaoyang District, Beijing 100123, China.
| | - Lei Tang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Radiology Department, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China.
| | - Zi-Yu Li
- Department of Gastrointestinal Cancer Center Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China.
| | - Xiao-Ting Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Radiology Department, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China.
| | - Hai-Feng Zhu
- Department of Radiology, Civil Aviation General Hospital, No. 1 Gaojingjia, Chaoyang Road, Chaoyang District, Beijing 100123, China.
| | - Ying-Shi Sun
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Radiology Department, Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China.
| | - Jia-Fu Ji
- Department of Gastrointestinal Cancer Center Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, No. 52 Fu-Cheng Road, Hai-Dian District, Beijing 100142, China.
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Roy AC, Shapiro J, Burge M, Karapetis CS, Pavlakis N, Segelov E, Chau I, Lordick F, Chen LT, Barbour A, Tebbutt N, Price T. Management of early-stage gastro-esophageal cancers: expert perspectives from the Australasian Gastrointestinal Trials Group (AGITG) with invited international faculty. Expert Rev Anticancer Ther 2020; 20:305-324. [PMID: 32202178 DOI: 10.1080/14737140.2020.1746185] [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: 10/24/2022]
Abstract
Introduction: A multimodal approach in operable early-stage oesophago-gastric (OG) cancer has evolved in the last decade, leading to improvement in overall outcomes.Areas covered: A review of the published literature and conference abstracts was undertaken on the topic of optimal adjunctive chemotherapy or chemoradiotherapy in early-stage OG cancers. This review article focuses on the current evidence pertaining to neoadjuvant and perioperative strategies in curable OG cancers including the evolving landscape of immunotherapy and targeted drugs in this setting.Expert commentary: Adjunctive therapies in the form of preoperative chemo-radiotherapy (CRT) or chemotherapy and perioperative chemotherapy over surgery alone improve outcomes in patients with operable OG cancer. Although there are variations in practice around the world, a multi-disciplinary approach to patient care is of paramount importance. Immunotherapy and on treatment functional imaging are two examples of emerging strategies to improve the outcome for early-stage patients. A better understanding of the molecular biology of this disease may help overcome the problem of tumor heterogeneity and enable more rationally designed and targeted therapeutic interventions in the future.
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Affiliation(s)
- Amitesh C Roy
- Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, Australia
| | | | - Matt Burge
- Department of Cancer Care Services, Royal Brisbane Hospital, University Of Queensland, Herston, Australia
| | - Christos S Karapetis
- Flinders Centre for Innovation in Cancer, Flinders University, Bedford Park, Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia
| | - Eva Segelov
- Department of Medical Oncology, Monash University and Monash Health, Melbourne, Australia
| | - Ian Chau
- Department of Medical Oncology, Royal Marsden Hospital, Institute of Cancer Research, Surrey, London, UK
| | - Florian Lordick
- Leipzig University Medical Centre, University Cancer Centre Leipzig, Leipzig, Germany
| | - Li-Tong Chen
- National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan
| | - Andrew Barbour
- The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, Australia
| | - Niall Tebbutt
- Department of Medical Oncology, Austin Health, Heidelberg, Australia
| | - Tim Price
- Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia
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FDG uptake reflects breast cancer immunological features: the PD-L1 expression and degree of TILs in primary breast cancer. Breast Cancer Res Treat 2020; 181:331-338. [PMID: 32253685 DOI: 10.1007/s10549-020-05619-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 03/26/2020] [Indexed: 01/22/2023]
Abstract
BACKGROUND High F18-fluorodeoxyglucose (FDG) uptake has been reported to be a predictor of poor prognosis in patients with breast cancer. We investigated the relationship between FDG uptake and immunological factors, including the data of programmed cell death-ligand 1 (PD-L1), CD8, and tumor-infiltrating lymphocytes (TILs). METHODS Breast cancer tissues of 97 patients who underwent surgery without preoperative therapy were examined. The grade of stromal TILs was immunohistochemically evaluated using the criteria of the International TILs Working Group in breast cancer. PD-L1 positivity and CD8 positivity were immunohistochemically evaluated. The FDG uptakes were evaluated based on the standardized uptake value max (SUVmax). The relationships between SUVmax and TIL grade and expression of PD-L1 and CD8 were investigated. RESULTS Among the 97 patients, 41 (42.3%) had a high SUVmax in their primary tumor, based on the SUVmax cut-off value 3 yielded by receiver operating characteristic curves. PD-L1 was positive in 17 patients (17.5%). Our analyses revealed that large tumor size, high nuclear grade, high degree of TILs and positive expression of PD-L1 were significantly associated with high SUVmax in the primary tumor. There were significant associations between SUVmax and the degree of TILs (r = 0.428, p < 0.001) and between SUVmax and the PD-L1 positivity (r = 0.413, p < 0.001). All cases with a high degree of TILs showed high CD8 expression. CONCLUSION Our results indicate that the FDG uptake may be predictive of immunological features including TILs and PD-L1 expression in breast cancer patients. Additional research is necessary to further evaluate FDG-PET as a biomarker of immune checkpoint therapy in breast cancer.
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14
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Faraji F, Gaba RC. Radiologic Modalities and Response Assessment Schemes for Clinical and Preclinical Oncology Imaging. Front Oncol 2019; 9:471. [PMID: 31214510 PMCID: PMC6558006 DOI: 10.3389/fonc.2019.00471] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Accepted: 05/16/2019] [Indexed: 11/29/2022] Open
Abstract
Clinical drug trials for oncology have resulted in universal protocols for medical imaging in order to standardize protocols for image procurement, radiologic interpretation, and therapeutic response assessment. In recent years, there has been increasing interest in using large animal models to study oncologic disease, though few standards currently exist for imaging of large animal models. This article briefly reviews medical imaging modalities, the current state-of-the-art in radiologic diagnostic criteria and response assessment schemes for evaluating therapeutic response and disease progression, and translation of radiologic imaging protocols and standards to large animal models of malignant disease.
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Affiliation(s)
- Farshid Faraji
- University of Illinois College of Medicine, Chicago, IL, United States
| | - Ron C Gaba
- Department of Radiology, University of Illinois Health, Chicago, IL, United States
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15
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Abstract
Multimodality therapy is the standard of care for locoregional esophageal cancers (greater than clinical T3 or Nþ), including Siewert type 1 and 2 gastroesophageal junction tumors. Induction regimen, chemotherapy only or chemoradiation, is an area of controversy and often institution-specific, as neither has shown to be superior. Response to induction therapy is an important prognostic marker. For esophageal squamous cell carcinoma, it may be acceptable to observe clinical complete responders after chemoradiotherapy and perform salvage esophagectomy for recurrent disease. Clinical T2N0 esophageal cancer presents a unique challenge given its inaccuracy in clinical staging; management of this particular subset is controversial.
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Affiliation(s)
- Matthew R Egyud
- Department of Surgery, Boston University School of Medicine, 88 East Newton Street, Collamore C-500, Boston, MA 02118, USA
| | - Jennifer F Tseng
- Department of Surgery, Boston University School of Medicine, Boston Medical Center, 88 East Newton Street, Collamore C-500, Boston, MA 02118, USA.
| | - Kei Suzuki
- Department of Surgery, Boston University School of Medicine, Boston Medical Center, 88 East Newton Street, Robinson 7280, Boston, MA 02118, USA
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16
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Borggreve AS, Goense L, Brenkman HJF, Mook S, Meijer GJ, Wessels FJ, Verheij M, Jansen EPM, van Hillegersberg R, van Rossum PSN, Ruurda JP. Imaging strategies in the management of gastric cancer: current role and future potential of MRI. Br J Radiol 2019; 92:20181044. [PMID: 30789792 DOI: 10.1259/bjr.20181044] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Accurate preoperative staging of gastric cancer and the assessment of tumor response to neoadjuvant treatment is of importance for treatment and prognosis. Current imaging techniques, mainly endoscopic ultrasonography (EUS), computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET), have their limitations. Historically, the role of magnetic resonance imaging (MRI) in gastric cancer has been limited, but with the continuous technical improvements, MRI has become a more potent imaging technique for gastrointestinal malignancies. The accuracy of MRI for T- and N-staging of gastric cancer is similar to EUS and CT, making MRI a suitable alternative to other imaging strategies. There is limited evidence on the performance of MRI for M-staging of gastric cancer specifically, but MRI is widely used for diagnosing liver metastases and shows potential for diagnosing peritoneal seeding. Recent pilot studies showed that treatment response assessment as well as detection of lymph node metastases and systemic disease might benefit from functional MRI (e.g. diffusion weighted imaging and dynamic contrast enhancement). Regarding treatment guidance, additional value of MRI might be expected from its role in better defining clinical target volumes and setup verification with MR-guided radiation treatment.
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Affiliation(s)
- Alicia S Borggreve
- 1 Department of Surgery, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands.,2 Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Lucas Goense
- 1 Department of Surgery, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands.,2 Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Hylke J F Brenkman
- 1 Department of Surgery, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Stella Mook
- 2 Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Gert J Meijer
- 2 Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Frank J Wessels
- 3 Department of Radiology, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Marcel Verheij
- 4 Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL) , Amsterdam , Netherlands
| | - Edwin P M Jansen
- 4 Department of Radiation Oncology, Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL) , Amsterdam , Netherlands
| | - Richard van Hillegersberg
- 1 Department of Surgery, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Peter S N van Rossum
- 2 Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
| | - Jelle P Ruurda
- 1 Department of Surgery, University Medical Center Utrecht, Utrecht University , Utrecht , Netherlands
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Comparing PET/MRI with PET/CT for Pretreatment Staging of Gastric Cancer. Gastroenterol Res Pract 2019; 2019:9564627. [PMID: 30863443 PMCID: PMC6378050 DOI: 10.1155/2019/9564627] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 10/19/2018] [Accepted: 11/08/2018] [Indexed: 12/13/2022] Open
Abstract
18F-FDG PET/MRI has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MRI in gastric cancer are rare because of motion artifacts. We investigated the value of PET/MRI for preoperative staging compared with PET/CT in gastric cancer (GC). Thirty patients with confirmed GC underwent PET/CT and PET/MRI. TNM staging for each patient was determined from the PET/MRI and PET/CT images. The diagnostic performance of PET/MRI and PET/CT was calculated compared with the pathologic TNM stage. The two methods were compared using statistical analyses. The accuracy for T staging between PET/MRI and PET/CT was 76.9% vs. 57.7%, respectively. In T1 and T4a staging, the sensitivity and specificity for PET/MRI vs. PET/CT was 1.0 vs. 0.6 and 1.0 vs. 0.8, respectively. The area under the curve (AUC) for PET/MRI vs. PET/CT was 1.00 vs. 0.78 in the T1 stage, 0.73 vs. 0.66 in the T2 stage, 0.72 vs. 0.57 in the T3 stage, and 0.86 vs. 0.83 in the T4 stage. The accuracy for N staging of PET/MRI vs. PET/CT was 53.9% vs. 34.0%, and that for N0 vs. N+ was 85.0% vs. 77.0%. The sensitivity for PET/MRI in N3 staging was 0.67 and 0 for PET/CT. There was a statistically significant difference in the AUC for N1 staging (PET/MRI vs. PET/CT, 0.63 vs. 0.53, p = 0.03). SUVmax/ADC positively correlated with tumor volume and Ki-67. PET/MRI performs more accurately in TNM staging compared with PET/CT and is optimal for accurate N staging. SUVmax/ADC has positive correlations with tumor volume and Ki-67.
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18
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Sada YH, Smaglo BG, Tan JC, Tran Cao HS, Musher BL, Massarweh NN. Prognostic Value of Nodal Response After Preoperative Treatment of Gastric Adenocarcinoma. J Natl Compr Canc Netw 2019; 17:161-168. [PMID: 30787129 DOI: 10.6004/jnccn.2018.7093] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Accepted: 10/04/2018] [Indexed: 12/20/2022]
Abstract
Background: Pathologically positive lymph nodes (ypN+) after preoperative chemotherapy are associated with poor survival in patients with gastric cancer. Little is known about the association between response to preoperative therapy and the benefit of postoperative therapy. Methods: This retrospective cohort study of the National Cancer Database included patients with clinically node-positive (cN+) gastric cancer treated with preoperative therapy followed by surgery (2006-2014). Preoperative treatment modality was categorized as the inclusion of radiation therapy (RT) or chemotherapy alone. Pretreatment clinical and pathologic stages were used to determine pathologic treatment response rates. The association between overall risk of death and preoperative treatment, disease response, and adjuvant therapy use was evaluated using multivariable Cox regression. Results: Preoperative RT was used in 53.6% of 1,976 patients with cN+ gastric cancer, (74.3% cardia and 10.1% noncardia). The nodal response rate was 38.9% and was higher with RT than with chemotherapy alone (cardia, 46.0% vs 29.1%; P<.001; noncardia, 43.8% vs 31.9%; P=.06). Preoperative RT was associated with an approximate 2-fold increase in the odds of pathologic response compared with chemotherapy. Overall, use of adjuvant therapy was not associated with a decreased risk of death. A primary tumor response with residual nodal disease was not associated with survival (hazard ratio [HR], 1.03; 95% CI, 0.66-1.60). However, a nodal response with residual primary disease was significantly associated with survival (HR, 0.54; 95% CI, 0.44-0.65). Conclusions: More than one-third of node-positive gastric cancers showed pathologic nodal response with preoperative treatment. RT is associated with a higher response than chemotherapy. Patients with ypN+ disease have worse survival, regardless of whether they receive postoperative therapy. Future gastric cancer trials should evaluate the role of preoperative RT and individualize postoperative therapy use.
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Affiliation(s)
- Yvonne H Sada
- aCenter for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.,bDepartment of Medicine, Baylor College of Medicine, Houston, Texas
| | - Brandon G Smaglo
- bDepartment of Medicine, Baylor College of Medicine, Houston, Texas
| | - Joy C Tan
- cBaylor College of Medicine, Houston, Texas; and
| | - Hop S Tran Cao
- dDepartment of Surgery, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas
| | | | - Nader N Massarweh
- aCenter for Innovations in Quality, Effectiveness, and Safety, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.,dDepartment of Surgery, Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas
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19
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Gao X, Zhang Y, Yuan F, Ding B, Ma Q, Yang W, Yan J, Du L, Wang B, Yan F, Sedlmair M, Pan Z, Zhang H. Locally advanced gastric cancer: total iodine uptake to predict the response of primary lesion to neoadjuvant chemotherapy. J Cancer Res Clin Oncol 2018; 144:2207-2218. [PMID: 30094537 DOI: 10.1007/s00432-018-2728-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2018] [Accepted: 07/30/2018] [Indexed: 12/22/2022]
Abstract
PURPOSE Pathologic response to neoadjuvant chemotherapy is a prognostic factor in many cancer types. However, the existing evaluative criteria are deficient. We sought to prospectively evaluate the total iodine uptake derived from dual-energy computed tomography (DECT) in predicting treatment efficacy and progression-free survival (PFS) time in gastric cancer after neoadjuvant chemotherapy. METHODS From October 2012 to December 2015, 44 patients with locally advanced gastric cancer were examined with DECT 1 week before and three cycles after neoadjuvant chemotherapy. The percentage changes in tumor area (%ΔS), diameter (%ΔD), and density (%ΔHU) were calculated to evaluate the WHO, RESCIST, and Choi criteria. The percentage changes in tumor volume (%ΔV) and total iodine uptake of portal phase (%ΔTIU-p) were also calculated to determine cut-off values by ROC curves. The correlation between the different criteria and histopathologic tumor regression grade (Becker score) or PFS were statistically analyzed. RESULTS Forty-four patients were divided into responders and non-responders according to 43.34% volume reduction (P = 0.002) and 63.87% (P = 0.002) TIU-p reduction, respectively. The %ΔTIU-p showed strong (r = 0.602, P = 0.000) and %ΔV showed moderate (r = 0.416, P = 0.005), while the WHO (r = 0.075, P = 0.627), RECIST (r = 0.270, P = 0.077) and Choi criteria (r = 0.238, P = 0.120) showed no correlation with the Becker score. The differences in PFS time between the responder and non-responder groups were significant according to %ΔTIU-p and Choi criteria (P = 0.001 and P = 0.013, respectively). CONCLUSIONS The TIU-p can help predict pathological regression in advanced gastric cancer patients after neoadjuvant chemotherapy. In addition, the %ΔTIU-p could be one of the potentially valuable predictive parameters of the PFS time.
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Affiliation(s)
- Xiaoyuan Gao
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Yang Zhang
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Fei Yuan
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Bei Ding
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Qianchen Ma
- Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Wenjie Yang
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Jing Yan
- Siemens Medical System, Shanghai, 201318, China
| | - Lianjun Du
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Baisong Wang
- Department of Biological Statistics, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China
| | - Fuhua Yan
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China
| | - Martin Sedlmair
- Computed Tomography Research and Development, Siemens Healthcare GmbH, Forchheim, Germany
| | - Zilai Pan
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China.
| | - Huan Zhang
- Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin 2nd Road, Shanghai, 200025, China.
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Heger U, Sisic L, Nienhüser H, Blank S, Hinz U, Haag GM, Ott K, Ulrich A, Büchler MW, Schmidt T. Neoadjuvant Therapy Improves Outcomes in Locally Advanced Signet-Ring-Cell Containing Esophagogastric Adenocarcinomas. Ann Surg Oncol 2018; 25:2418-2427. [PMID: 29855828 DOI: 10.1245/s10434-018-6541-3] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Only a few studies have analyzed multimodal treatment concepts in the subgroup of signet-ring-cell containing upper gastrointestinal (GI) cancer. Recent retrospective, multicentric data favor primary resection without neoadjuvant chemotherapy for gastric signet-ring-cell containing carcinomas (SRCs). We compared the outcomes of primarily resected carcinomas with neoadjuvantly treated, locally advanced esophagogastric SRCs. METHODS A total of 310 patients with esophagogastric SRC-staged cT3/4/Nany/Many from a prospective unicentric database were included in this study; 192 (61.9%) received neoadjuvant therapy (NEO group) and 118 (38.1%) were primarily resected (RES group). RESULTS Overall, 128 (41.3%) patients presented with adenocarcinoma of the esophagogastric junction (AEG) and 182 (58.7%) presented with gastric cancer. Neoadjuvant therapy was significantly associated with resection in curative intent (NEO: 91.1%; RES: 75.4%; P = 0.001), improved (y)pT category (P = 0.035), improved (y)pN category (P < 0.001), and R0 resections (curative intent cohort: 76.0% in NEO vs. 60.7% in RES; P = 0.010), among others, but not with postoperative complications. Overall survival was significantly improved by neoadjuvant treatment {median survival 28.5 months (95% confidence interval [CI] 14.4-39.6) vs. RES: 14.9 months (10.6-17.5); P < 0.001}, as well as in subgroups (AEG and gastric tumors, R0-resected patients, and patients with and without relevant comorbidities). Independent prognostic factors were neoadjuvant therapy (hazard ratio [HR] 0.66; P = 0.023), pT4 category (HR 1.71; P = 0.041), pN2 category (HR 1.86; P = 0.013), pN3 category (HR 2.40; P < 0.001), pM1 category (HR 1.95; P = 0.003), age > 70 years (HR 1.79; P = 0.006), gastric localization (HR 0.69; P = 0.032), American Society of Anesthesiologists classification 3/4 (HR 1.71; P = 0.004), and incomplete resection R1/2 (HR 1.6; P = 0.014). CONCLUSIONS Our results demonstrate a survival advantage for advanced-stage esophagogastric SRC patients by neoadjuvant treatment.
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Affiliation(s)
- Ulrike Heger
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Leila Sisic
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Henrik Nienhüser
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Susanne Blank
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Ulf Hinz
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Georg Martin Haag
- National Center for Tumor Diseases (NCT), University Hospital, Heidelberg, Germany
| | - Katja Ott
- Department of Surgery, RoMed Klinikum, Rosenheim, Germany
| | - Alexis Ulrich
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Markus W Büchler
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplant Surgery, University Hospital, Heidelberg, Germany.
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21
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Cartwright E, Keane FK, Enzinger PC, Hong T, Chau I. Is There a Precise Adjuvant Therapy for Esophagogastric Carcinoma? Am Soc Clin Oncol Educ Book 2018; 38:280-291. [PMID: 30231360 DOI: 10.1200/edbk_200785] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Esophagogastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis for patients with locally advanced disease is poor and the majority of patients with operable tumors treated with surgery alone will have recurrent disease. A multimodal approach to treatment with adjunctive chemotherapy or chemoradiotherapy is therefore the standard of care for these patients. However, there is no global consensus on the optimal treatment strategy and international guidelines vary. National clinical trials inform local practice: neoadjuvant, perioperative, and adjuvant chemotherapy and radiotherapy combinations are all possible treatment options in the management of resectable esophagogastric cancer. A number of clinical trials are ongoing, which seek to directly compare multimodal treatment options and hope to provide clarity in this area. Furthermore, increased understanding of the molecular and genetic features of esophagogastric cancer may help to guide management of operable disease by determining optimal patient selection through identification of predictive biomarkers of response and the application of novel targeted agents.
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Affiliation(s)
- Elizabeth Cartwright
- From the Royal Marsden Hospital, London, United Kingdom; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Royal Marsden Hospital, Surrey, United Kingdom
| | - Florence K Keane
- From the Royal Marsden Hospital, London, United Kingdom; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Royal Marsden Hospital, Surrey, United Kingdom
| | - Peter C Enzinger
- From the Royal Marsden Hospital, London, United Kingdom; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Royal Marsden Hospital, Surrey, United Kingdom
| | - Theodore Hong
- From the Royal Marsden Hospital, London, United Kingdom; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Royal Marsden Hospital, Surrey, United Kingdom
| | - Ian Chau
- From the Royal Marsden Hospital, London, United Kingdom; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Royal Marsden Hospital, Surrey, United Kingdom
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22
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Gastric Cancer Maximum Tumour Diameter Reduction Rate at CT Examination as a Radiological Index for Predicting Histopathological Regression after Neoadjuvant Treatment: A Multicentre GIRCG Study. Gastroenterol Res Pract 2018; 2018:1794524. [PMID: 29736166 PMCID: PMC5875045 DOI: 10.1155/2018/1794524] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2017] [Accepted: 12/24/2017] [Indexed: 12/20/2022] Open
Abstract
Aim To investigate the role of maximum tumour diameter (D-max) reduction rate at CT examination in predicting histopathological tumour regression grade (TRG according to the Becker grade), after neoadjuvant chemotherapy (NAC), in patients with resectable advanced gastric cancer (AGC). Materials and Methods Eighty-six patients (53 M, mean age 62.1 years) with resectable AGC (≥T3 or N+), treated with NAC and radical surgery, were enrolled from 5 centres of the Italian Research Group for Gastric Cancer (GIRCG). Staging and restaging CT and histological results were retrospectively reviewed. CT examinations were contrast enhanced, and the stomach was previously distended. The D-max was measured using 2D software and compared with Becker TRG. Statistical data were obtained using “R” software. Results The interobserver agreement was good/very good. Becker TRG was predicted by CT with a sensitivity and specificity, respectively, of 97.3% and 90.9% for Becker 1 (D-max reduction rate > 65.1%), 76.4% and 80% for Becker 3 (D-max reduction rate < 29.9%), and 70.8% and 83.9% for Becker 2. Correlation between radiological and histological D-max measurements was strongly confirmed by the correlation index (c.i.= 0.829). Conclusions D-max reduction rate in AGC patients may be helpful as a simple and reproducible radiological index in predicting TRG after NAC.
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23
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Lee S, Choi S, Kim SY, Yun MJ, Kim HI. Potential Utility of FDG PET-CT as a Non-invasive Tool for Monitoring Local Immune Responses. J Gastric Cancer 2017; 17:384-393. [PMID: 29302378 PMCID: PMC5746659 DOI: 10.5230/jgc.2017.17.e43] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 12/22/2017] [Accepted: 12/22/2017] [Indexed: 01/15/2023] Open
Abstract
Purpose The tumor microenvironment is known to be associated with the metabolic activity of cancer cells and local immune reactions. We hypothesized that glucose metabolism measured by 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) (18F-FDG PET-CT) would be associated with local immune responses evaluated according to the presence of tumor infiltrating lymphocytes (TILs). Materials and Methods We retrospectively reviewed 56 patients who underwent 18F-FDG PET-CT prior to gastrectomy. In resected tumor specimens, TIL subsets, including cluster of differentiation (CD) 3, CD4, CD8, Forkhead box P3 (Foxp3), and granzyme B, were subjected to immunohistochemical analysis. The prognostic nutritional index (PNI) was calculated as: (10×serum albumin value)+(0.005×peripheral lymphocyte counts). Additionally, the maximum standard uptake value (SUVmax) was calculated to evaluate the metabolic activity of cancer cells. Results The SUVmax was positively correlated with larger tumor size (R=0.293; P=0.029) and negatively correlated with PNI (R=−0.407; P=0.002). A higher SUVmax showed a marginal association with higher CD3 (+) T lymphocyte counts (R=0.227; P=0.092) and a significant association with higher Foxp3 (+) T lymphocyte counts (R=0.431; P=0.009). No other clinicopathological characteristics were associated with SUVmax or TILs. Survival analysis, however, indicated that neither SUVmax nor Foxp3 held prognostic significance. Conclusions FDG uptake on PET-CT could be associated with TILs, especially regulatory T cells, in gastric cancer. This finding may suggest that PET-CT could be of use as a non-invasive tool for monitoring the tumor microenvironment in patients with gastric cancer.
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Affiliation(s)
- Seungho Lee
- Department of Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea
| | - Seohee Choi
- Department of Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea
| | - Sang Yong Kim
- Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.,Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei University Health System, Seoul, Korea
| | - Mi Jin Yun
- Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Hyoung-Il Kim
- Department of Surgery, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea.,Medical Research Center, Yonsei University College of Medicine, Seoul, Korea.,Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei University Health System, Seoul, Korea
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24
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Lee SY, Seo HJ, Kim S, Eo JS, Oh SC. Prognostic significance of interim 18 F-fluorodeoxyglucose positron emission tomography-computed tomography volumetric parameters in metastatic or recurrent gastric cancer. Asia Pac J Clin Oncol 2017; 14:e302-e309. [PMID: 29226597 DOI: 10.1111/ajco.12833] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 11/02/2017] [Indexed: 01/02/2023]
Abstract
AIM To evaluate the prognostic role of interim analysis of 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) volumetric parameters in patients with recurrent or metastatic advanced gastric cancer (AGC) treated with fluoropyrimidine-based palliative chemotherapy. METHODS Forty-four patients who underwent baseline and interim PET/CT scanning during palliative chemotherapy were analyzed retrospectively. Initial and change of metabolic parameters (MP) - metabolic tumor volume (MTV), tumor lesion glycolysis (TLG) and maximum and mean standardized uptake values (SUV) were measured with PET/CT. Metabolic change was measured by ∆MP (%) = (MPinterim - MPinitial )/MP initial × 100. Independent t-test was employed to compare values of initial, interim and change of metabolic parameters between each response group. Log-rank test was employed for univariate analysis, and multivariate analysis was performed using the Cox proportional hazards regression model to determine independently significant prognostic factors. RESULTS Reduced percentage values of maximum and mean SUV on interim PET/CT and initial values of volumetric parameters (MTV and TLG) were significant predicting factors to response to fluoropyrimidine-based palliative chemotherapy. The decreased percentage values of metabolic parameters as well as maximum and mean SUV with receiver operating characteristic (ROC) curve determined cut-off points were significant prognostic factors for overall survival and progression-free survival in univariate and multivariate analyses. CONCLUSION Measurement of metabolic decrease of volumetric parameters by interim PET/CT analysis is useful to determine the prognosis of patients with recurrent or metastatic AGC.
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Affiliation(s)
- Suk-Young Lee
- Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyo Jung Seo
- Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sungeun Kim
- Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jae Seon Eo
- Department of Nuclear Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Cheul Oh
- Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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25
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Abstract
Oesophageal cancer is a clinically challenging disease that requires a multidisciplinary approach. Extensive treatment might be associated with a considerable decline in health-related quality of life and yet still a poor prognosis. In recent decades, prognosis has gradually improved in many countries. Endoscopic procedures have increasingly been used in the treatment of premalignant and early oesophageal tumours. Neoadjuvant therapy with chemotherapy or chemoradiotherapy has supplemented surgery as standard treatment of locally advanced oesophageal cancer. Surgery has become more standardised and centralised. Several therapeutic alternatives are available for palliative treatment. This Seminar aims to provide insights into the current clinical management, ongoing controversies, and future needs in oesophageal cancer.
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Affiliation(s)
- Jesper Lagergren
- Division of Cancer Studies, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK; Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
| | - Elizabeth Smyth
- Department of Gastrointestinal Oncology, The Royal Marsden NHS Foundation Trust, London, UK
| | - David Cunningham
- Department of Gastrointestinal Oncology, The Royal Marsden NHS Foundation Trust, London, UK
| | - Pernilla Lagergren
- Surgical Care Science, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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26
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Huang EP, Lin FI, Shankar LK. Beyond Correlations, Sensitivities, and Specificities: A Roadmap for Demonstrating Utility of Advanced Imaging in Oncology Treatment and Clinical Trial Design. Acad Radiol 2017; 24:1036-1049. [PMID: 28456570 DOI: 10.1016/j.acra.2017.03.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2016] [Revised: 01/05/2017] [Accepted: 03/02/2017] [Indexed: 12/13/2022]
Abstract
Despite the widespread belief that advanced imaging should be very helpful in guiding oncology treatment decision and improving efficiency and success rates in treatment clinical trials, its acceptance has been slow. Part of this is likely attributable to gaps in study design and statistical methodology for these imaging studies. Also, results supporting the performance of the imaging in these roles have largely been insufficient to justify their use within the design of a clinical trial or in treatment decision making. Statistically significant correlations between the imaging results and clinical outcomes are often incorrectly taken as evidence of adequate performance. Assessments of whether the imaging can outperform standard techniques or meaningfully supplement them are also frequently neglected. This paper provides guidance on study designs and statistical analyses for evaluating the performance of advanced imaging in the various roles in treatment decision guidance and clinical trial conduct. Relevant methodology from the imaging literature is reviewed; gaps in the literature are addressed using related concepts from the more extensive genomic and in vitro biomarker literature.
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Affiliation(s)
- Erich P Huang
- Biometric Research Program, Division of Cancer Treatment, Diagnosis National Cancer Institute, NIH, 9609 Medical Center Drive, MSC 9735, Bethesda, MD 20892-9735.
| | - Frank I Lin
- Cancer Imaging Program, Division of Cancer Treatment, Diagnosis National Cancer Institute, NIH, Bethesda, Maryland
| | - Lalitha K Shankar
- Cancer Imaging Program, Division of Cancer Treatment, Diagnosis National Cancer Institute, NIH, Bethesda, Maryland
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De Souza K, Atabani S, Madhusudan S. Precision medicine in gastric cancer: where are we now? EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2017. [DOI: 10.1080/23808993.2017.1357431] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Karen De Souza
- Department of Oncology, Nottingham University Hospitals, Nottingham, UK
| | - Suha Atabani
- Department of Oncology, Nottingham University Hospitals, Nottingham, UK
| | - Srinivasan Madhusudan
- Department of Oncology, Nottingham University Hospitals, Nottingham, UK
- Translational Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK
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28
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Tahara T, Shibata T, Okubo M, Yoshida D, Kawamura T, Horiguchi N, Ishizuka T, Nagasaka M, Nakagawa Y, Ohmiya N. Histological evaluations of primary lesions are independently associated with prognosis in patients with gastric cancer who receive neoadjuvant chemotherapy. Oncol Lett 2017; 13:4892-4896. [PMID: 28599492 DOI: 10.3892/ol.2017.6040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 02/23/2017] [Indexed: 02/06/2023] Open
Abstract
Neoadjuvant chemotherapy may improve outcomes for patients with locally advanced gastric cancer (GC). To explore useful predictive factors for the response of advanced GC to neoadjuvant chemotherapy, tumor responses were assessed using computed tomography (CT) with histological based criteria. A total of 78 patients with advanced GC undergoing neoadjuvant chemotherapy were included. CT-based response assessment was performed following 2 courses of treatment. Histological evaluation of resected specimens was also performed according to the Japanese classification of gastric carcinoma. Grade 1b, 2 and 3 (viable tumor cells remaining in <2/3 of the tumorous area) were defined as histological responders. The results were associated with overall survival (OS) and progression-free survival (PFS). The majority of the cases underwent tegafur/gimeracil/oteracil based preoperative chemotherapy as the first line of treatment (n=76, 96%). A total of 25 (32%) and 29 (37%) cases were considered to be CT and histological responders, respectively. CT-based evaluation was not associated with OS or PFS, while histological evaluation was significantly associated with OS and PFS. Histological based evaluation was not associated with CT and GI X-ray or endoscopy-based evaluation of primary lesions. Multivariate survival analysis using Cox's regression model demonstrated that histological non-response was an independent prognostic factor for predicting worse OS. Histological-based evaluation of primary lesions was independently associated with prognosis in patients with GC who underwent neoadjuvant chemotherapy.
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Affiliation(s)
- Tomomitsu Tahara
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Tomoyuki Shibata
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Masaaki Okubo
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Dai Yoshida
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Tomohiko Kawamura
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Noriyuki Horiguchi
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Takamitsu Ishizuka
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Mitsuo Nagasaka
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Yoshihito Nakagawa
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
| | - Naoki Ohmiya
- Department of Gastroenterology, Fujita Health University School of Medicine, Toyoake, Aichi 470-1192, Japan
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29
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Yip C, Weeks A, Shaw K, Siddique M, Chang F, Landau DB, Cook GJ, Goh V. Magnetic Resonance Imaging (MRI) of Intratumoral Voxel Heterogeneity as a Potential Response Biomarker: Assessment in a HER2+ Esophageal Adenocarcinoma Xenograft Following Trastuzumab and/or Cisplatin Therapy. Transl Oncol 2017; 10:459-467. [PMID: 28456115 PMCID: PMC5408154 DOI: 10.1016/j.tranon.2017.03.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 03/21/2017] [Accepted: 03/21/2017] [Indexed: 01/16/2023] Open
Abstract
We evaluated magnetic resonance imaging (MRI) voxel heterogeneity following trastuzumab and/or cisplatin in a HER2+ esophageal xenograft (OE19) as a potential response biomarker. OE19 xenografts treated with saline (controls), monotherapy, or combined cisplatin and trastuzumab underwent 9.4-T MRI. Tumor MRI parametric maps of T1 relaxation time (pre/post contrast), T2 relaxation time, T2* relaxation rate (R2*), and apparent diffusion coefficient obtained before (TIME0), after 24hours (TIME1), and after 2weeks of treatment (TIME2) were analyzed. Voxel histogram and fractal parameters (from the whole tumor, rim and center, and as a ratio of rim-to-center) were derived. Tumors were stained for immunohistochemical markers of hypoxia (CA-IX), angiogenesis (CD34), and proliferation (Ki-67). Combination therapy reduced xenograft growth rate (relative change, ∆ +0.58±0.43 versus controls, ∆ +4.1±1.0; P=0.008). More spatially homogeneous voxel distribution between the rim to center was noted after treatment for combination therapy versus controls, respectively, for contrast-enhanced T1 relaxation time (90th percentile: ratio 1.00 versus 0.88, P=0.009), T2 relaxation time (mean: 1.00 versus 0.92, P=0.006; median: 0.98 versus 0.91, P=0.006; 75th percentile: 1.02 versus 0.94, P=0.007), and R2* (10th percentile: 0.99 versus 1.26, P=0.003). We found that combination and trastuzumab monotherapy reduced MRI spatial heterogeneity and growth rate compared to the control or cisplatin groups, the former providing adjunctive tumor response information.
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Affiliation(s)
- Connie Yip
- Department of Cancer Imaging, Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK; Department of Radiation Oncology, National Cancer Centre, 11 Hospital Drive 169610, Singapore.
| | - Amanda Weeks
- Department of Cancer Imaging, Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK
| | - Karen Shaw
- Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK
| | - Musib Siddique
- Department of Cancer Imaging, Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK
| | - Fuju Chang
- Department of Histopathology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London SE1 7EH, UK
| | - David B Landau
- Department of Clinical Oncology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London SE1 7EH, UK
| | - Gary Jr Cook
- Department of Cancer Imaging, Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK; Clinical PET Imaging Centre, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London SE1 7EH, UK
| | - Vicky Goh
- Department of Cancer Imaging, Division of Imaging Sciences & Biomedical Engineering, King's College London, St Thomas' Hospital, London SE1 7EH, UK; Department of Radiology, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London SE1 7EH, UK
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30
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Zhou J, Shen J, Seifer BJ, Jiang S, Wang J, Xiong H, Xie L, Wang L, Sui X. Approaches and genetic determinants in predicting response to neoadjuvant chemotherapy in locally advanced gastric cancer. Oncotarget 2017; 8:30477-30494. [PMID: 27802185 PMCID: PMC5444758 DOI: 10.18632/oncotarget.12955] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2015] [Accepted: 10/18/2016] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer remains a major health burden worldwide. There is near-universal agreement that neoadjuvant chemotherapy (NAC) is a preferred management for locally advanced gastric cancer (LAGC). However, the optimal approach for an individual patient is still not clear and remains controversial, which could be at least partly explained by the lack of predictive tools. The ability to predict chemosensitivity from NAC in routine clinical practice is difficult and is an area of intense investigation, especially in the Precision-Medicine Era. Available consistent evidence suggests that a favorable tumor histopathological response to NAC may be a useful positive prognostic marker in gastric cancer. Hence, it is reasonable to speculate that making the histopathological response from NAC predictable will dramatically facility the NAC and improve patients' outcome. This review provides an overview on the current status of predictive biomarkers for histopathological response from NAC in LAGC, including clinicopathological variables, imaging and molecular testing. Furthermore, limitations and future perspectives are also discussed.
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Affiliation(s)
- Jichun Zhou
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Jianguo Shen
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Benjamin J. Seifer
- Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Shaojie Jiang
- Department of Radiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
| | - Ji Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Hanchu Xiong
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Lingmin Xie
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Linbo Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
| | - Xinbing Sui
- Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, Zhejiang, China
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China
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Prior JO, Gillessen S, Wirth M, Dale W, Aapro M, Oyen WJ. Radiopharmaceuticals in the elderly cancer patient: Practical considerations, with a focus on prostate cancer therapy. Eur J Cancer 2017; 77:127-139. [DOI: 10.1016/j.ejca.2017.01.030] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Revised: 01/12/2017] [Accepted: 01/29/2017] [Indexed: 11/24/2022]
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Abstract
Gastric cancer represents a major cause of cancer mortality worldwide despite a declining incidence. New molecular classification schemes developed from genomic and molecular analyses of gastric cancer have provided a framework for understanding this heterogenous disease, and early findings suggest these classifications will be relevant for designing and implementing new targeted therapies. The success of targeted therapy and immunotherapy in breast cancer and melanoma, respectively, has not been duplicated in gastric cancer, but trastuzumab and ramucirumab have demonstrated efficacy in select populations. New markers that predict therapeutic response are needed to improve patient selection for both targeted and immunotherapies.
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Affiliation(s)
- Matthew S Strand
- Department of Surgery, Barnes-Jewish Hospital and Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA
| | - Albert Craig Lockhart
- Department of Medicine, Barnes-Jewish Hospital and Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8056, St Louis, MO 63110, USA
| | - Ryan C Fields
- Department of Surgery, Barnes-Jewish Hospital and Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St Louis, MO 63110, USA.
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Kim TH, Kim J, Kang YK, Lee M, Kim HS, Cheon GJ, Chung HH. Identification of Metabolic Biomarkers Using Serial 18F-FDG PET/CT for Prediction of Recurrence in Advanced Epithelial Ovarian Cancer. Transl Oncol 2017; 10:297-303. [PMID: 28314183 PMCID: PMC5361859 DOI: 10.1016/j.tranon.2017.02.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 01/31/2017] [Accepted: 02/06/2017] [Indexed: 11/02/2022] Open
Abstract
PURPOSE To evaluate the prognostic value of metabolic parameters derived from serial 18F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with advanced epithelial ovarian cancer (EOC). METHODS Thirteen patients with advanced EOC who received surgical staging and adjuvant platinum-based combination chemotherapy were prospectively enrolled. 18F-FDG PET/CT was performed before and after the surgical staging, and after third cycle of chemotherapy. Tumor glucose metabolism at baseline and its change after operation and third cycle of chemotherapy such as changes of maximum standardized uptake values (ΔSUVmax) via 18F-FDG PET/CT were measured, and assessed regarding their ability to predict recurrence. RESULTS Median duration of progression-free survival (PFS) was 25 months (range, 13-34), and although optimal debulking was performed in 10 patients, 5 (38.5%) patients experienced recurrence. Univariate analyses showed significant associations between recurrence and low ΔSUVmax after surgical staging, and low SUVmax change after third cycle of chemotherapy. Multivariate analysis identified low ΔSUVmax after third cycle of chemotherapy as an independent risk factor for recurrence (P=.047, hazard ratio (HR) 16.375, 95% CI 1.041-257.536). Kaplan-Meier survival curves showed that PFS significantly differed in groups categorized based on ΔSUVmax after chemotherapy (P=.001, log-rank test). CONCLUSIONS 18F-FDG PET/CT allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after chemotherapy. The metabolic response measured as ΔSUVmax after third cycle of chemotherapy appears to be promising predictor of recurrence in patients with advanced EOC.
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Affiliation(s)
- Tae Hun Kim
- Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Seoul, Republic of Korea
| | - Junhwan Kim
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Yeon-Koo Kang
- Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Maria Lee
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hee Seung Kim
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Gi Jeong Cheon
- Department of Nuclear Medicine, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyun Hoon Chung
- Department of Obstetrics and Gynecology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
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Manoharan V, Lee S, Chong S, Yap J, Coupe N, Wilson R, Merrett N, Ng W, Lin M. Serial imaging using [18F]Fluorodeoxyglucose positron emission tomography and histopathologic assessment in predicting survival in a population of surgically resectable distal oesophageal and gastric adenocarcinoma following neoadjuvant therapy. Ann Nucl Med 2017; 31:315-323. [PMID: 28299585 PMCID: PMC5397458 DOI: 10.1007/s12149-017-1159-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Accepted: 02/13/2017] [Indexed: 12/13/2022]
Abstract
Background and objectives We retrospectively evaluated the value of PET/CT in predicting survival and histopathological tumour-response in patients with distal oesophageal and gastric adenocarcinoma following neoadjuvant treatment. Methods Twenty-one patients with resectable distal oesophageal adenocarcinoma and 14 with gastric adenocarcinoma between January 2002 and December 2011, who had undergone serial PET before and after neoadjuvant therapy followed by surgery, were enrolled. Maximum standard uptake value (SUVmax) and metabolic tumour volume were measured and correlated with tumour regression grade and survival. Results Histopathological tumour response (PR) is a stronger predictor of overall and disease-free survival compared to metabolic response. ∆%SUVmax ≥70% was the only PET metric that predicted PR (82.4% sensitivity, 61.5% specificity, p = 0.047). Histopathological non-responders had a higher risk of death (HR 8.461, p = 0.001) and recurrence (HR 6.385, p = 0.002) and similarly in metabolic non-responders for death (HR 2.956, p = 0.063) and recurrence (HR 3.614, p = 0.028). Ordinalised ∆%SUVmax showed a predictive trend for OS and DFS, but failed to achieve statistical significance. Conclusions PR was a stronger predictor of survival than metabolic response. ∆%SUVmax ≥70% was the best biomarker on PET that predicted PR and survival in oesophageal and gastric adenocarcinoma. Ordinalisation of ∆%SUVmax was not helpful in predicting primary outcomes.
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Affiliation(s)
- Varun Manoharan
- University of New South Wales, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Soon Lee
- University of Western Sydney, Liverpool Hospital, Sydney, NSW, 2170, Australia.,Department of Anatomical Pathology, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Shanley Chong
- University of New South Wales, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - June Yap
- Department of Nuclear Medicine and PET, Ground Floor, New Clinical Building, 1 Elizabeth Drive, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Nick Coupe
- Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Robert Wilson
- University of New South Wales, Liverpool Hospital, Sydney, NSW, 2170, Australia.,Department of Surgery, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Neil Merrett
- University of Western Sydney, Liverpool Hospital, Sydney, NSW, 2170, Australia.,Department of Surgery, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Weng Ng
- University of New South Wales, Liverpool Hospital, Sydney, NSW, 2170, Australia.,Department of Medical Oncology, Liverpool Hospital, Sydney, NSW, 2170, Australia
| | - Michael Lin
- University of New South Wales, Liverpool Hospital, Sydney, NSW, 2170, Australia. .,University of Western Sydney, Liverpool Hospital, Sydney, NSW, 2170, Australia. .,Department of Nuclear Medicine and PET, Ground Floor, New Clinical Building, 1 Elizabeth Drive, Liverpool Hospital, Sydney, NSW, 2170, Australia.
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Celli R, Colunga M, Patel N, Djekidel M, Jain D. Metabolic Signature on 18F-FDG PET/CT, HER2 Status, and Survival in Gastric Adenocarcinomas. J Nucl Med Technol 2016; 44:234-238. [PMID: 27789750 DOI: 10.2967/jnmt.116.181479] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 10/14/2016] [Indexed: 12/23/2022] Open
Abstract
The human epidermal growth factor 2 (HER2)-overexpressing (HER2-positive [HER2+]) gastric (GC) and gastroesophageal junction adenocarcinomas (GEJC) are felt to represent a more aggressive form of disease, which may correlate to increased metabolic activity. Whether tumor SUVmax measured by 18F-FDG PET/CT could be a preoperative parameter used to predict HER2 status of GC/GEJC is unknown. METHODS Pathology reports of HER2+ GC/GEJC biopsies and resections from 31 patients were reviewed and compared with HER2-negative (HER2-) cases distributed evenly over the same time period. We analyzed their SUVmax intensity and then compared the HER2 status and SUVmax parameters and their association with survival. RESULTS After matching for age and sex, there was no difference in SUVmax between HER2+ and HER2- cases (9.7 and 8.4, respectively; P = 0.6). No difference was seen between HER2+ and HER2- cases in tumor histology (81% and 57% intestinal type, respectively; P = 0.11), size (2.6 and 3.8 cm, respectively; P = 0.12), differentiation (47% and 68% poorly differentiated, respectively; P = 0.06), or presence of lymph node metastasis (60% and 40%, respectively; P = 0.3). Although there was no difference in survival demonstrated by HER2+ and HER2- cases, there was a significant difference in survival between SUVmax above (12.2 mo) and below (30 mo) the median SUVmax (6.6, P = 0.01). CONCLUSION Our study shows that SUVmax is not associated with HER2 status of GC/GEJC. Independent of HER2 overexpression, patients with a high SUVmax demonstrate a worse overall survival, suggesting that metabolic signature is a better predictor of biologic tumor aggressiveness than its histologic signature.
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Affiliation(s)
- Romulo Celli
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
| | | | - Natalie Patel
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
| | | | - Dhanpat Jain
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut
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Won E, Shah MA, Schöder H, Strong VE, Coit DG, Brennan MF, Kelsen DP, Janjigian YY, Tang LH, Capanu M, Rizk NP, Allen PJ, Bains MS, Ilson DH. Use of positron emission tomography scan response to guide treatment change for locally advanced gastric cancer: the Memorial Sloan Kettering Cancer Center experience. J Gastrointest Oncol 2016; 7:506-14. [PMID: 27563439 DOI: 10.21037/jgo.2016.06.01] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non-responders. METHODS Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m(2), cisplatin 60 mg/m(2) day 1, and capecitabine 625 mg/m(2) bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., ≥35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m(2), irinotecan 50 mg/mg(2) day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders. RESULTS Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30-85%] in responders compared with 56% in the non-responder group (95% CI, 20-80%, P=0.93). CONCLUSIONS The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial.
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Affiliation(s)
- Elizabeth Won
- Department of Medicine/Gastrointestinal Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Manish A Shah
- Department of Medicine/Gastrointestinal Medical Oncology, Weill-Cornell Medical College/New York Presbyterian Hospital, New York, USA
| | - Heiko Schöder
- Department of Radiology/Nuclear Medicine, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Vivian E Strong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Daniel G Coit
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Murray F Brennan
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - David P Kelsen
- Department of Medicine/Gastrointestinal Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Yelena Y Janjigian
- Department of Medicine/Gastrointestinal Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Laura H Tang
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Marinela Capanu
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Nabil P Rizk
- Department of Surgery, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601, USA
| | - Peter J Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Manjit S Bains
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | - David H Ilson
- Department of Medicine/Gastrointestinal Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, USA
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Zhou JC, Guo JF, Teng RY, Wang QC, Wang J, Wei Q, Li ZD, Shen JG, Wang LB. New utility of an old marker: serum low-density lipoprotein predicts histopathological response of neoadjuvant chemotherapy in locally advanced gastric cancer. Onco Targets Ther 2016; 9:5041-7. [PMID: 27574445 PMCID: PMC4990386 DOI: 10.2147/ott.s97061] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Although the correlation between metabolic abnormality and gastric cancer has been extensively investigated, the question of whether metabolic parameters might influence the efficacy of chemotherapy in locally advanced gastric cancer is still unanswered. In our present study, we investigated the relationship between serum fasting glucose, lipid levels, and histopathological response of neoadjuvant chemotherapy (NAC) in locally advanced gastric cancers. Patients and methods A total of 128 patients were identified from a prospectively maintained database of patients with locally advanced gastric cancer who received NAC between July 2004 and December 2012. Histopathological response after NAC was analyzed according to Becker’s tumor-regression grade. Univariate analyses and multivariable regression analyses were performed to determine the correlation between tumor size, differentiation, fasting glucose, lipid levels, and tumor histopathological response after NAC. Results Univariate analysis revealed that low-density lipoprotein level and total cholesterol, as well as tumor size and differentiation, correlated significantly with histopathological response. Low-density lipoprotein levels and tumor size were found to be independent predictors for histopathological response, according to multivariable regression analyses. Conclusion In this observational, hypothesis-generating study, serum low-density lipoprotein measurement was found to be useful in predicting chemosensitivity to locally advanced gastric cancer patients undergoing NAC. Incorporation of serum low-density lipoprotein levels into individualized treatment protocols could be considered in clinical practice.
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Affiliation(s)
- Ji-Chun Zhou
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Ju-Feng Guo
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Surgical Oncology, Hangzhou First People's Hospital, Hangzhou, People's Republic of China
| | - Rong-Yue Teng
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Qin-Chuan Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Ji Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Qun Wei
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of International Medicine and Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Zi-Duo Li
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Dendritic Cell Biology and Therapeutic Group, ANZAC Research Institute, University of Sydney, Sydney, NSW, Australia
| | - Jian-Guo Shen
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Lin-Bo Wang
- Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, People's Republic of China
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dos Anjos RF, dos Anjos DA, Vieira DL, Leite AF, Figueiredo PTDS, de Melo NS. Effectiveness of FDG-PET/CT for evaluating early response to induction chemotherapy in head and neck squamous cell carcinoma: A systematic review. Medicine (Baltimore) 2016; 95:e4450. [PMID: 27512861 PMCID: PMC4985316 DOI: 10.1097/md.0000000000004450] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND F-Fluoro-Deoxy-Glucose Positron Emission Tomography with Computed Tomography (F-FDG PET/CT) may be a powerful tool to predict treatment outcome. We aimed to review the effectiveness of F-FDG PET/CT in the assessment of early response to induction chemotherapy (IC) in patients with advanced Head and Neck Squamous Cell Cancer (HNSCC) without previous treatment. METHODS PubMed, Cochrane Library, Science Direct and Web of Science were searched to May 2016. Reference lists of the included articles and additional studies identified by one nuclear medicine expert were screened for potential relevant studies that investigated the effectiveness of F-FDG PET/CT performed before and after IC. Three authors independently screened all retrieved articles, selected studies that met inclusion criteria and extracted data. The methodology of the selected studies was evaluated by using the risk of bias checklist of the Agency for Healthcare Research and Quality (AHRQ). RESULTS Seven out of 170 eligible studies met our inclusion criteria. A total of 207 advanced HNSCC patients were evaluated with F-FDG PET/CT at baseline and after IC in the selected articles. Six from seven studies concluded that F-FDG PET/CT allowed early evaluation response to IC and predicted survival outcomes. CONCLUSION The present systematic review confirms the potential value of F-FDG PET/CT as a diagnostic tool for early IV response assessment in HNSCC patients. However, the lack of standard definitions for response criteria and heterogeneous IC protocols indicate the need to further studies in order to better define the role of F-FDG PET/CT in these patients.
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Wang X, Zhao L, Liu H, Zhong D, Liu W, Shan G, Dong F, Gao W, Bai C, Li X. A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer. Br J Cancer 2016; 114:1326-33. [PMID: 27172250 PMCID: PMC4984457 DOI: 10.1038/bjc.2016.126] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Revised: 03/11/2016] [Accepted: 04/18/2016] [Indexed: 02/07/2023] Open
Abstract
Background: We evaluated the efficacy and safety of the modified FOLFOX6 (mFOLFOX6) regimen as
a neoadjuvant chemotherapy in gastric cancer patients. Methods: Seventy-three patients with T2–T4 or N+ were enroled. Preoperative
chemotherapy consisted of three cycles of mFOLFOX6. The primary end points were
the response rate and the R0 resection rate. Prognostic factors for overall
survival (OS) were investigated using univariate and multivariate analyses. Results: Sixty-seven (91.8%) patients completed 3 cycles, with grade 3–4
toxicity arising in 33.0%. The radiology response rate was 45.8%.
Sixty-seven (91.8%) patients receiving radical surgery showed different
levels of histological regression of the primary tumour, with a ⩾50%
regression rate of 49.2%. ypTNM stage (HR 4.045, 95% CI
1.429–11.446) and tumours of diffuse and mixed type (HR 9.963, 95% CI
1.937–51.235; HR 8.890, 95% CI 1.157–68.323, respectively) were
significantly associated with OS. The pathologic regression rate (GHR;
⩾2/3/<2/3, ⩾50%/<50%) was
statistically significantly associated with OS according to a univariate
analysis. Conclusions: Perioperative mFOLFOX6 was a tolerable and effective regimen for gastric cancer.
The ypTNM stage was an independent predictor of survival. GHR
⩾50%/<50% could be used as a surrogate marker for
selecting a postoperative chemotherapy regimen.
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Affiliation(s)
- Xiang Wang
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100032, China
| | - Lin Zhao
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100032, China
| | - Hongfeng Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Dingrong Zhong
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Wei Liu
- Department of Radiation, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Guangliang Shan
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Fen Dong
- Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of basic Medicine, Peking Union Medical College, Beijing 100005, China
| | - Weisheng Gao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100032, China
| | - Xiaoyi Li
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China
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Büyükdereli G, Güler M, Şeydaoğlu G. Interobserver and Intraobserver Variability among Measurements of FDG PET/CT Parameters in Pulmonary Tumors. Balkan Med J 2016; 33:308-15. [PMID: 27308075 DOI: 10.5152/balkanmedj.2016.140530] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 06/26/2015] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND 18F-fluorodeoxyglucose (FDG) positron emission tomography computed tomography (PET/CT) provides information about metabolic and morphologic status of malignancies. Tumor size and standardized uptake value (SUV) measurements are crucial for cancer treatment monitoring. AIMS The purpose of our study was to assess the variability of these measurements performed by observers evaluating lung tumors. STUDY DESIGN Retrospective cross-sectional study. METHODS FDG PET/CT images of 97 patients with pulmonary tumors were independently evaluated by two experienced nuclear medicine physicians. Primary tumor size (UDCT), maximum SUV (SUVmax), mean SUV (SUVmean) and maximum SUV normalized to liver mean SUV (SUVnliv max) were measured by each observer at two different times with an interval of at least 2 weeks. Interobserver and intraobserver variabilities of measurements were evaluated through statistical methods. RESULTS Size of the lesions varied from 0.81 to 13.6 cm (mean 4.29±2.24 cm). Very good agreement was shown with correlation, Bland-Altman and regression analysis for all measured PET/CT parameters. In the interobserver and intraobserver variability analysis, the Pearson correlation coefficients were greater than 0.96 and 0.98, respectively. CONCLUSION Semi-quantitative measurements of pulmonary tumors were highly reproducible when determined by experienced physicians with clinically available software for routine FDG PET/CT evaluation. Consistency may be improved if the same observer performs serial measurements for any one patient.
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Affiliation(s)
- Gülgün Büyükdereli
- Department of Nuclear Medicine, Çukurova University School of Medicine, Adana, Turkey
| | - Mehtap Güler
- Department of Nuclear Medicine, State Hospital, Niğde, Turkey
| | - Gülşah Şeydaoğlu
- Department of Biostatistics, Çukurova University School of Medicine, Adana, Turkey
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Pak K, Kim SJ. What Do We Measure in Oncology PET? Nucl Med Mol Imaging 2016; 51:212-216. [PMID: 28878846 DOI: 10.1007/s13139-016-0416-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 03/08/2016] [Accepted: 04/01/2016] [Indexed: 12/13/2022] Open
Abstract
Positron emission tomography (PET) has come to the practice of oncology. It is known that 18F-fluorodeoxyglucose (FDG) PET is more sensitive for the assessment of treatment response than conventional imaging. In addition, PET has an advantage in the use of quantitative analysis of the study. Nowadays, various PET parameters are adopted in clinical settings. In addition, a wide range of factors has been known to be associated with FDG uptake. Therefore, there has been a need for standardization and harmonization of protocols and PET parameters. We will introduce PET parameters and discuss major issues in this review.
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Affiliation(s)
- Kyoungjune Pak
- Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Seong-Jang Kim
- Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.,Department of Nuclear Medicine and Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Pusan National University, Yangsan, Korea
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Blank S, Knebel P, Haag GM, Bruckner T, Klaiber U, Burian M, Schaible A, Sisic L, Schmidt T, Diener MK, Ott K. Immediate tumor resection in patients with locally advanced gastroesophageal adenocarcinoma with nonresponse to chemotherapy after 4 weeks of treatment versus resection after completion of chemotherapy (OPTITREAT trial, DRKS00004668): study protocol for a randomized controlled pilot trial. Pilot Feasibility Stud 2016; 2:18. [PMID: 27965838 PMCID: PMC5153833 DOI: 10.1186/s40814-016-0059-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Accepted: 03/08/2016] [Indexed: 12/22/2022] Open
Abstract
Background Neoadjuvant chemotherapy is a standard of care for patients with adenocarcinoma of the esophagus and stomach in Europe, but still only 20–40 % respond to therapy and the critical issue; how to treat nonresponding patients is still unclear. So far, there is no randomized trial evaluating the impact of early termination of neoadjuvant chemotherapy and immediate tumor resection in nonresponding patients with locally advanced gastroesophageal cancer on postoperative outcome. With this exploratory pilot trial, we want to get first estimates about the effect of discontinuation of chemotherapy with the aim to plan and conduct a further definitive trial. Methods/design OPTITREAT is designed as a single-center, randomized controlled pilot trial with two parallel study groups. Four weeks after starting neoadjuvant chemotherapy in all patients, clinical response will be assessed by endoscopy and endosonographic ultrasound. Then, nonresponding patients (n = 84) will be randomized in a 1:1 ratio to intervention group with stopping chemotherapy and immediate tumor resection or control group with completion of chemotherapy before surgery. Outcome measures are overall survival, R0 resection rate, perioperative morbidity and mortality, histopathological response, and quality of life. Statistical analysis will be based on the intention-to-treat population. Due to the study design as an explorative pilot trial, no formal sample size calculation was performed. The planned total sample size of 120 patients is considered ethical and large enough to show the feasibility and safety of the concept. First data on differences between the study groups in the defined endpoints will also be generated. Discussion Individualized therapy is of utmost interest in the treatment of locally advanced gastroesophageal adenocarcinoma as less than half of the patients show objective response to current chemotherapy regimens. The findings of the OPTITREAT trial will help to get first data about clinical response evaluation followed by immediate tumor resection in nonresponding patients after 4 weeks of neoadjuvant chemotherapy. Based on the results of this pilot study, a future confirmatory trial will be planned to prove efficacy and evaluate significance. Trial registration German Clinical Trial Register number: DRKS00004668
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Affiliation(s)
- Susanne Blank
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany
| | - Phillip Knebel
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany.,Study Centre of the German Surgical Society (SDGC), University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany
| | - Georg-Martin Haag
- Department of Medical Oncology, National Center of Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, Heidelberg, 69120 Germany
| | - Thomas Bruckner
- Institute of Medical Statistics and Informatics, University of Heidelberg, Im Neuenheimer Feld 305, Heidelberg, 69120 Germany
| | - Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany
| | - Maria Burian
- Department of General Visceral and Transplantation Surgery, Endoscopic Center, University of Gießen, Rudolf-Buchheimstr. 7, Gießen, 35392 Germany
| | - Anja Schaible
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany.,Interdisciplinary Endoscopic Center, University of Heidelberg, Im Neuenheimer Feld 460, Heidelberg, 69120 Germany
| | - Leila Sisic
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany
| | - Markus K Diener
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany.,Study Centre of the German Surgical Society (SDGC), University of Heidelberg, Im Neuenheimer Feld 110, Heidelberg, 69120 Germany
| | - Katja Ott
- Department of Surgery, RoMed Klinikum, Pettenkoferstr. 10, Rosenheim, 83022 Germany
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Kim YW, Kim MJ, Ryu KW, Lim HS, Lee JH, Kong SY, Lee JS, Choi IJ, Kim CG, Lee JY, Cho SJ, Kook MC, Park YI, Kim SK, Park SR. A phase II study of perioperative S-1 combined with weekly docetaxel in patients with locally advanced gastric carcinoma: clinical outcomes and clinicopathological and pharmacogenetic predictors for survival. Gastric Cancer 2016; 19:586-596. [PMID: 25851942 DOI: 10.1007/s10120-015-0490-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Accepted: 03/13/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome. METHODS Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2) twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1. RESULTS From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes. CONCLUSION Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.
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Affiliation(s)
- Young-Woo Kim
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Mi-Jung Kim
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Keun Won Ryu
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Hyeong-Seok Lim
- Department of Laboratory Medicine, Center for Diagnostic Oncology, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea.,Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jun Ho Lee
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Sun-Young Kong
- Department of Laboratory Medicine, Center for Diagnostic Oncology, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Jong Seok Lee
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Il Ju Choi
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Chan Gyoo Kim
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Jong Yeul Lee
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Soo-Jeong Cho
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Myeong-Cherl Kook
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Young-Iee Park
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Seok-Ki Kim
- Department of Nuclear Medicine, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea
| | - Sook Ryun Park
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Republic of Korea. .,Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro, 43-gil, Songpa-gu, Seoul, 138-736, Republic of Korea.
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Multiparametric fully-integrated 18-FDG PET/MRI of advanced gastric cancer for prediction of chemotherapy response: a preliminary study. Eur Radiol 2015; 26:2771-8. [DOI: 10.1007/s00330-015-4105-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Revised: 08/20/2015] [Accepted: 11/10/2015] [Indexed: 01/08/2023]
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Lee JW, Lee SM, Son MW, Lee MS. Diagnostic performance of FDG PET/CT for surveillance in asymptomatic gastric cancer patients after curative surgical resection. Eur J Nucl Med Mol Imaging 2015; 43:881-888. [PMID: 26611426 DOI: 10.1007/s00259-015-3249-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 10/30/2015] [Indexed: 12/25/2022]
Abstract
PURPOSE The present study evaluated the diagnostic performance of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) for surveillance in asymptomatic gastric cancer patients after curative surgical resection. METHODS We retrospectively recruited 190 gastric cancer patients (115 early gastric cancer patients and 75 advanced gastric cancer patients) who underwent 1-year (91 patients) or 2-year (99 patients) postoperative FDG PET/CT surveillance, along with a routine follow-up program, after curative surgical resection. All enrolled patients were asymptomatic and showed no recurrence on follow-up examinations performed before PET/CT surveillance. All PET/CT images were visually assessed and all abnormal findings on follow-up examinations including FDG PET/CT were confirmed with histopathological diagnosis or clinical follow-up. RESULTS During follow-up, 19 patients (10.0 %) developed recurrence. FDG PET/CT showed abnormal findings in 37 patients (19.5 %). Among them, 16 patients (8.4 %) were diagnosed as cancer recurrence. Of 153 patients without abnormal findings on PET/CT, three patients were false-negative and diagnosed as recurrence on other follow-up examinations. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG PET/CT were 84.2 %, 87.7 %, 43.2 %, and 98.0 %, respectively. Among 115 early gastric cancer patients, PET/CT detected recurrence in four patients (3.5 %) and one patient with local recurrence. Among 75 advanced gastric cancer patients, PET/CT detected recurrence in 12 patients (16.0 %), excluding two patients experiencing peritoneal recurrence. In addition, FDG PET/CT detected secondary primary cancer in six (3.2 %) out of all the patients. CONCLUSIONS Post-operative FDG PET/CT surveillance showed good diagnostic ability for detecting recurrence in gastric cancer patients. FDG PET/CT could be a useful follow-up modality for gastric cancer patients, especially those with advanced gastric cancer. However, further careful evaluation is needed because of false-positive findings on PET/CT.
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Affiliation(s)
- Jeong Won Lee
- Department of Nuclear Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Sang Mi Lee
- Department of Nuclear Medicine, Soonchunhyang University Hospital, 23-20 Byeongmyeong-dong, Dongnam-gu, Chungcheongnam-do, Cheonan, Korea, 330-721.
| | - Myoung Won Son
- Department of Surgery, Soonchunhyang University Hospital, Cheonan, Korea
| | - Moon-Soo Lee
- Department of Surgery, Soonchunhyang University Hospital, Cheonan, Korea
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Incremental diagnostic utility of gastric distension FDG PET/CT. Eur J Nucl Med Mol Imaging 2015; 43:644-53. [PMID: 26487512 DOI: 10.1007/s00259-015-3211-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 09/28/2015] [Indexed: 12/19/2022]
Abstract
PURPOSE To assess the diagnostic utility of gastric distension (GD) FDG PET/CT in both patients with known gastric malignancy and those not known to have gastric malignancy but with incidental focal FDG uptake in the stomach. METHODS This retrospective analysis included 88 patients who underwent FDG PET/CT following GD with hyoscine N-butylbromide (Buscopan®) and water ingestion as part of routine clinical evaluation between 2004 and 2014. FDG PET/CT scans before and after GD were reported blinded to the patient clinical details in 49 patients undergoing pretreatment staging of gastric malignancy and 39 patients who underwent GD following incidental suspicious gastric uptake. The PET findings were validated by a composite clinical standard. RESULTS In the 49 patients undergoing pretreatment staging of gastric malignancy, GD improved PET detection of the primary tumour (from 80 % to 90 %). PET evaluation of tumour extent was concordant with endoscopic/surgical reports in 31 % (interpreter 1) and 45 % (interpreter 2) using pre-GD images and 73 % and 76 % using GD images. Interobserver agreement also improved with GD (κ = 0.29 to 0.69). Metabolic and morphological quantitative analysis demonstrated a major impact of GD in normal gastric wall but no significant effect in tumour, except a minor increase in SUV related to a delayed acquisition time. The tumour to normal stomach SUVmax ratio increased from 3.8 ± 2.9 to 9.2 ± 8.6 (mean ± SD) with GD (p < 0.0001), facilitating detection and improved assessment of the primary tumour. In 25 (64 %) of the 39 patients with incidental suspicious gastric uptake, acquisition after GD correctly excluded a malignant process. In 10 (71 %) of the remaining 14 patients with persistent suspicious FDG uptake despite GD, malignancy was confirmed and in 3 (21 %) an active but benign pathology was diagnosed. CONCLUSION GD is a simple way to improve local staging with FDG PET in patients with gastric malignancy. In the setting of incidental suspicious gastric uptake, GD is also an effective tool for ruling out malignancy and leads to the avoidance of unnecessary endoscopy.
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Charalampakis N, Xiao L, Elimova E, Wadhwa R, Shiozaki H, Shimodaira Y, Blum MA, Planjery V, Rogers JE, Matamoros A, Sagebiel T, Das P, Lee JH, Bhutani MS, Weston B, Estrella JS, Badgwell BD, Ajani JA. Initial Standardized Uptake Value of Positron Emission Tomography Influences the Prognosis of Patients with Localized Gastric Adenocarcinoma Treated Preoperatively. Oncology 2015; 89:305-10. [PMID: 26393501 DOI: 10.1159/000436972] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Accepted: 06/16/2015] [Indexed: 12/21/2022]
Abstract
BACKGROUND In patients with localized gastric adenocarcinoma (LGAC) who receive preoperative therapy, tools to predict response or prognosticate outcome before therapy are lacking. We used initial standardized uptake value (iSUV) of positron emission tomography (PET) to evaluate its association with overall survival (OS). METHODS We identified 60 patients with confirmed LGAC who were treated with preoperative chemoradiation and had a baseline PET in addition to other routine staging. Fisher's exact test and Wilcoxon's rank sum test were used to determine the association between iSUV and other variables, and the log-rank test and Cox proportional hazards model were used for survival analysis. RESULTS The median iSUV was 6 (range, 0-28). The presence of signet ring cells in pretreatment biopsies correlated highly with low iSUV (≤ 6; p = 0.0017). Patients with a high iSUV (> 6) had a longer OS compared to those with a low iSUV (≤ 6; p = 0.0344). iSUV was not an independent predictor (p = 0.12); however, the risk of death was reduced for patients with an iSUV > 6 (hazard ratio = 0.26). CONCLUSION Our novel findings show that among LGAC patients treated with preoperative chemoradiation and surgery, those with a high iSUV have longer OS than patients with a low iSUV. iSUV appears to have a predictive role in patients with LGAC when treated with preoperative chemoradiation.
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Affiliation(s)
- Nikolaos Charalampakis
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Tex., USA
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Evaluating the response of gastric carcinomas to neoadjuvant chemotherapy using iodine concentration on spectral CT: a comparison with pathological regression. Clin Radiol 2015; 70:1198-204. [PMID: 26188843 DOI: 10.1016/j.crad.2015.06.083] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 06/09/2015] [Accepted: 06/18/2015] [Indexed: 02/08/2023]
Abstract
AIM To investigate the potential of iodine concentration (IC) determined using virtual monochromatic spectral computed tomography (CT) to predict the response of gastric carcinomas to preoperative neoadjuvant chemotherapy (NC). MATERIALS AND METHODS A total of 20 patients were enrolled who underwent two spectral CT examinations (1 week before and two cycles after NC). The percentage change in tumour thickness (%ΔCWT) and in IC on the arterial phase (%ΔIC-a) and venous phase (%ΔIC-v) after NC were calculated and compared for different histopathological regression grades and response groups. The diagnostic efficacies to discriminate good response (GR) and poor response (PR) of the above three parameters were evaluated using receiver operating characteristic (ROC) curves. RESULTS The decrease rate of %ΔIC-a for the GR group was higher than that for the PR group (-0.59 [-0.76, -0.20] versus -0.11 [-0.75, 0.92], p=0.012). There was no significant difference in the %ΔIC-v and %ΔCWT values between the GR and PR groups (p=0.076 and p=0.779, respectively). The areas under the ROC curve (AUC) values were 0.857, 0.762, and 0.542 for %ΔIC-a, %ΔIC-v, and %ΔCWT, respectively, in the response prediction. The cut-off value for identifying PR was a decrease rate of <52.9% for %ΔIC-a, and the sensitivity and specificity values were 0.857 and 0.833. CONCLUSION Changes in the IC for gastric carcinomas following NC were detected using spectral CT and correlated with histopathological regression. The prediction efficacy for IC was better than that for tumour thickness, with IC on the arterial phase being a better predictor than IC on the venous phase.
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Abstract
OBJECTIVE. The purpose of this study was to evaluate the repeatability of liver mean standardized uptake value normalized to lean body mass (SULmean) in the same patients at different time points within the right lobe of the liver at (18)F-FDG PET/CT, in a clinical setting. MATERIALS AND METHODS. Two PET/CT studies performed on two different dates from each of 130 patients who had normal livers according to structural imaging were included in this reader study. The mean (± SD) length of time between the studies was 235 ± 192 days. SULmean was measured with a 30-mm diameter spherical volume of interest (VOI) placed within the right lobe of the liver (above, below, and at the level of the main portal vein) by two expert readers. ANOVA, intraclass correlation coefficient (ICC), and Bland-Altman analysis were performed. RESULTS. The ICC for the first and second set of studies varied between 0.487 and 0.535 for reader 1 and between 0.472 and 0.545 for reader 2. The mean percentage variation for SULmean between the two time scans for the VOIs placed above, below, and at the level of the main portal vein were 3.55% ± 23.19%, 4.65% ± 23.87%, and 4.30% ± 23.03%, respectively, for reader 1 and 4.49% ± 23.23%, 4.33% ± 23.74%, and 4.48% ± 23.01%, respectively, for reader 2. Using 95% CI, the reference range for intrapatient variations between the studies in liver SULmean was -0.5 to 0.60. CONCLUSION. There is only fair repeatability of liver SULmean measured between two time points in the same patient in a clinical setting. Scan-to-scan intrapatient variation in absolute liver SULmean was -0.5 to 0.60.
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Altini C, Niccoli Asabella A, Di Palo A, Fanelli M, Ferrari C, Moschetta M, Rubini G. 18F-FDG PET/CT role in staging of gastric carcinomas: comparison with conventional contrast enhancement computed tomography. Medicine (Baltimore) 2015; 94:e864. [PMID: 25997066 PMCID: PMC4602890 DOI: 10.1097/md.0000000000000864] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
The purpose of the report was to evaluate the role of fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (F-FDG PET/CT) in staging gastric cancer comparing it with contrast enhancement computed tomography (CECT).This retrospective study included 45 patients who underwent performed whole body CECT and F-FDG PET/CT before any treatment. We calculated CECT and F-FDG PET/CT sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) for gastric, lymphnode, and distant localizations; furthermore, we compared the 2 techniques by McNemar test. The role of F-FDG PET/CT semiquantitative parameters in relation to histotype, grading, and site of gastric lesions were evaluated by ANOVA test.Sensitivity, specificity, accuracy, PPV and NPV of CECT, and F-FDG PET/CT for gastric lesion were, respectively, 92.11%, 57.14%, 86.66%, 92.11%, 57.14% and 81.58%, 85.71%, 82.22%, 96.88%, 46.15%. No differences were identified between the 2 techniques about sensitivity and specificity. No statistical differences were observed between PET parameters and histotype, grading, and site of gastric lesion. The results of CECT and F-FDG PET/CT about lymphnode involvement were 70.83%, 61.90%, 66.66%, 68%, 65% and 58.33%, 95.24%, 75.55%, 93.33%, 66.67%. The results of CECT and F-FDG PET/CT about distant metastases were 80%, 62.86%, 66.66%, 38.10%, 91.67% and 60%, 88.57%, 82.22%, 60%, 88.57%. FDG PET/CT specificity was significantly higher both for lymphnode and distant metastases.The F-FDG PET/CT is a useful tool for the evaluation of gastric carcinoma to detect primary lesion, lymphnode, and distant metastases using 1 single image whole-body technique. Integration of CECT with F-FDG PET/CT permits a more valid staging in these patients.
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Affiliation(s)
- Corinna Altini
- From the Nuclear Medicine Unit (CA, ANA, ADP, MF, CF, GR); Section of Diagnostic Imaging, D.I.M., University of Bari "Aldo Moro", Bari, Italy (MM)
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