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Gebauer F, Plum PS, Damanakis A, Chon SH, Popp F, Zander T, Quaas A, Fuchs H, Schmidt T, Schröder W, Bruns CJ. Long-Term Postsurgical Outcomes of Neoadjuvant Chemoradiation (CROSS) Versus Chemotherapy (FLOT) for Multimodal Treatment of Adenocarcinoma of the Esophagus and the Esophagogastric Junction. Ann Surg Oncol 2023; 30:7422-7433. [PMID: 37210683 PMCID: PMC10562333 DOI: 10.1245/s10434-023-13643-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 04/17/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND The question of the ideal neoadjuvant therapy for locally advanced esophagogastric adenocarcinoma has not been answered to date. Multimodal treatment has become a standard treatment for these adenocarcinomas. Currently, perioperative chemotherapy (FLOT) or neoadjuvant chemoradiation (CROSS) is recommended. METHODS A monocentric retrospective analysis compared long-term survival after CROSS versus FLOT. The study enrolled patients with adenocarcinoma of the esophagus (EAC) or the esophagogastric junction type I or II undergoing oncologic Ivor-Lewis esophagectomy between January 2012 and December 2019. The primary objective was to determine the long-term outcome in terms of overall survival. The secondary objectives were to determine differences regarding the histopathologic categories after neoadjuvant treatment and the histomorphologic regression. RESULTS The findings showed no survival advantage for one or the other treatment in this highly standardized cohort. All the patients underwent open (CROSS: 9.4% vs. FLOT: 22%), hybrid (CROSS: 82% vs. FLOT: 72%), or minimally invasive (CROSS: 8.9% vs. FLOT: 5.6%) thoracoabdominal esophagectomy. The median post-surgical follow-up period was 57.6 months (95% confidence interval [CI] 23.2-109.7 months), and the median survival was longer for the CROSS patients (54 months) than for the FLOT patients (37.2 months) (p = 0.053). The overall 5-years survival was 47% for the entire cohort (48% for the CROSS and 43% for the FLOT patients). The CROSS patients showed a better pathologic response and fewer advanced tumor stages. CONCLUSION The improved pathologic response after CROSS cannot be translated into longer overall survival. To date, the choice of which neoadjuvant treatment to use can be made only on the basis of clinical parameters and the patient's performance status.
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Affiliation(s)
- Florian Gebauer
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany
- Department of General and Visceral Surgery, Helios University Hospital of Wuppertal, Wuppertal, Germany
| | - Patrick S Plum
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany.
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany.
| | - Alexander Damanakis
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Seung-Hun Chon
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Felix Popp
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Thomas Zander
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany
- Department I of Internal Medicine, Faculty of Medicine, Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Germany
| | - Alexander Quaas
- Gastrointestinal Cancer Group Cologne (GCGC), Cologne, Germany
- Institute of Pathology, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Hans Fuchs
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Thomas Schmidt
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Wolfgang Schröder
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
| | - Christiane J Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, Faculty of Medicine, University Hospital Cologne, Cologne, Germany
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Zhu Y, Chen J, Sun X, Lou Y, Fang M, Zhou F, Zhang L, Xin Y. Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis. Front Oncol 2023; 13:1177557. [PMID: 37228495 PMCID: PMC10203550 DOI: 10.3389/fonc.2023.1177557] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 04/25/2023] [Indexed: 05/27/2023] Open
Abstract
Background There is increasing evidence that neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. However, a number of studies have come to the opposite conclusion. Therefore, our meta-analysis is to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Methods We searched Wanfang Database, China National Knowledge Network database, VIP database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library. The searched terms included'Stomach Neoplasms', 'Neoadjuvant Therapy' and 'Chemoradiotherapy'. The retrieval time was from the establishment of the corresponding database to September 2022, and our meta-analysis was performed using RevMan (version 5.3) and Stata (version 17) software. Results A total of 17 literatures were included, which involved 7 randomized controlled trials and 10 retrospective studies, with a total of 6831 patients. The results of meta-analysis showed that compared with NACT group, the complete response rate(RR=1.95, 95%CI 1.39-2.73, p=0.0001), the partial response rate(RR=1.44, 95%CI 1.22-1.71, p=0.0001), the objective response rate(RR=1.37, 95%CI 1.27-1.54, p=0.00001), the pathologic complete response rate(RR=3.39, 95%CI 2.17-5.30, p=0.00001), the R0 resection rate(RR=1.18, 95%CI 1.09-1.29, p=0.0001) and 3-year overall survival rate(HR=0.89, 95%CI 0.82-0.96, p=0.002) of neoadjuvant chemoradiotherapy group were significantly improved. The results of subgroup analyses of gastric cancer subgroup and gastroesophageal junction cancer subgroup were consistent with the overall results. Meanwhile, the stable disease(RR=0.59, 95%CI:0.44-0.81, P=0.0010) of neoadjuvant chemoradiotherapy group was lower than that of neoadjuvant chemotherapy group, and there were no statistical significance in the progressive disease rate(RR=0.57, 95%CI:0.31-1.03, P=0.06), five-year overall survival rate(HR=1.03, 95%CI:0.99-1.07, P=0.839), postoperative complications and adverse reactions between the neoadjuvant chemoradiotherapy group and neoadjuvant chemotherapy group. Conclusion Compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy might bring more survival benefits without significantly increasing adverse reactions. neoadjuvant chemoradiotherapy may be a recommended treatment for patients with locally advanced gastric cancer. Systematic Review Registration https://inplasy.com/inplasy-2022-12-0068/, identifier INPLASY202212068.
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Affiliation(s)
- Youqi Zhu
- Department of Radiation, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Jiuzhou Chen
- Department of Radiation, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Xueqing Sun
- Department of Radiation, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yufei Lou
- Department of Radiation, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Miao Fang
- Department of Radiation, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Fengjuan Zhou
- Department of Radiation, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Lei Zhang
- Department of Oncology, Suining County People’s Hospital, Xuzhou, Jiangsu, China
| | - Yong Xin
- Department of Radiation, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- Department of Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China
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Shao P, Nima S, Tse Y, Suolang Z, Pubu C. Multimodal treatments for resectable esophagogastric junction cancer: A Bayesian network meta-analysis. Langenbecks Arch Surg 2023; 408:123. [PMID: 36934163 DOI: 10.1007/s00423-023-02862-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 03/08/2023] [Indexed: 03/19/2023]
Abstract
PURPOSE To comprehensively investigate the optimal multimodal treatment of resectable esophagogastric junction (EGJ) cancer. METHODS PubMed, Embase, Cochrane Library and Web of Science were searched until March 11, 2022. The outcomes were overall survival (OS), locoregional and distant recurrence, and R0 resection. Network plots, forest plots and league tables were drawn for each outcome. Rank probabilities for different treatments in each outcome were also depicted. RESULTS A total of 23 studies with 18,319 EGJ participants were included. No significant differences in OS between any two of the 6 treatments. Perioperative chemoradiotherapy (pCRT) had the highest probability (36.03%) to be the optimal treatment as regards OS. Patients undergoing pCRT had a significantly lower incidence of locoregional recurrence than those undergoing adjuvant chemotherapy (aCT), neoadjuvant chemotherapy (nCT), perioperative chemotherapy (pCT), or surgery alone (S). Patients with pCRT had the greatest likelihood (68.86%) to have the lowest incidence of locoregional recurrence. Comparable impacts of the 6 treatments on the incidence of distant recurrence, and pCRT was most likely (46.65%) to be the optimal treatment with respect to distant recurrence. Neoadjuvant CRT (nCRT) was associated with a significantly increased incidence of R0 resection compared with nCT or S, and nCRT had the highest probability (97.68%) to be the best therapy regarding R0 resection. CONCLUSION For patients with resectable EGJ cancer, pCRT may be the optimal multimodal treatment regarding survival and recurrence.
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Affiliation(s)
- Pengfei Shao
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Shazhen Nima
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Yang Tse
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Zhuoma Suolang
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China
| | - Cangjue Pubu
- Gastroenterology Department, Lhasa People's Hospital, No.1 Beijing East Road, Chengguan District, Lhasa, 850000, Tibet Autonomous Region, China.
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Kitagawa Y, Ishihara R, Ishikawa H, Ito Y, Oyama T, Oyama T, Kato K, Kato H, Kawakubo H, Kawachi H, Kuribayashi S, Kono K, Kojima T, Takeuchi H, Tsushima T, Toh Y, Nemoto K, Booka E, Makino T, Matsuda S, Matsubara H, Mano M, Minashi K, Miyazaki T, Muto M, Yamaji T, Yamatsuji T, Yoshida M. Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1. Esophagus 2023:10.1007/s10388-023-00993-2. [PMID: 36933136 PMCID: PMC10024303 DOI: 10.1007/s10388-023-00993-2] [Citation(s) in RCA: 147] [Impact Index Per Article: 73.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 02/27/2023] [Indexed: 03/19/2023]
Affiliation(s)
- Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
| | - Ryu Ishihara
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hitoshi Ishikawa
- QST Hospital, National Institutes for Quantum Science and Technology, Chiba, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine, Tokyo, Japan
| | - Takashi Oyama
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, International University of Health and Welfare School of Medicine, Chiba, Japan
| | - Tsuneo Oyama
- Department of Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan
| | - Ken Kato
- Department Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | | | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Hiroshi Kawachi
- Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shiko Kuribayashi
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Koji Kono
- Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan
| | - Takashi Kojima
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Hiroya Takeuchi
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Takahiro Tsushima
- Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yasushi Toh
- National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Kenji Nemoto
- Department of Radiology, Yamagata University Graduate School of Medicine, Yamagata, Japan
| | - Eisuke Booka
- Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan
| | - Tomoki Makino
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan
| | - Hisahiro Matsubara
- Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Masayuki Mano
- Department of Central Laboratory and Surgical Pathology, National Hospital Organization Osaka National Hospital, Osaka, Japan
| | - Keiko Minashi
- Clinical Trial Promotion Department, Chiba Cancer Center, Chiba, Japan
| | - Tatsuya Miyazaki
- Department of Surgery, Japanese Red Cross Maebashi Hospital, Gunma, Japan
| | - Manabu Muto
- Department of Clinical Oncology, Kyoto University Hospital, Kyoto, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Tomoki Yamatsuji
- Department of General Surgery, Kawasaki Medical School, Okayama, Japan
| | - Masahiro Yoshida
- Department of Hepato-Biliary-Pancreatic and Gastrointestinal Surgery, School of Medicine, International University of Health and Welfare Ichikawa Hospital, Chiba, Japan
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Wu L, Xing Z, Huang M, Yu H, Qin Y, Jin Q, Zhou Z, Chen J. Nodal downstaging to ypN0 after neoadjuvant chemotherapy positively impacts on survival of cT4N+ GC/GEJ patients. J Surg Oncol 2022; 126:1403-1412. [PMID: 36001384 DOI: 10.1002/jso.27065] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 07/24/2022] [Accepted: 08/01/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND The prognostic value of histomorphologic regression in primary gastric and gastroesophageal cancers (GC/GEJ) has been previously established, however, the impact of lymph node (LN) regression on survival still remains unclear. METHODS A prospectively maintained database was reviewed to identify cT4N+ gastric and gastroesophageal cancers (GC/GEJ) after NAC (neoadjuvant chemotherapy). Patients were categorized into two groups based on LN status: cN+/ypN0 (downstaged N0) and cN+/ypN+ (persistent N+), long-term survival were analyzed using Kaplan-Meier survival estimates. RESULTS In total, 125 patients with cT4N+ GC/GEJ underwent NAC followed by surgery were enrolled. A total of 39 patients (31.2%) had cN+/ypN0 (ypN0) disease, 86 patients (68.8%) had cN+/ypN+ (ypN+) disease. Prognosis in ypN+ patients was significantly worse than those in ypN0 group for 3- and 5-year overall survival (OS) (p < 0.05). The 3-year OS was 83%, 44% in ypN0 and ypN+ group, respectively. The 5-year OS was 75%, 35% in ypN0 and ypN+ group, respectively. Multivariable analysis suggested that multivisceral resection (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.14-0.76, p = 0.009), and ypN+ (HR = 3.42, 95% CI: 1.15-10.13, p =0.027) were independent prognostic factors for OS. CONCLUSION Nodal downstaging is an important hallmark representing the effectiveness of NAC for GC/GEJ, and it positively impacts on survival of these patients.
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Affiliation(s)
- Liucheng Wu
- Department of Gastrointestinal Surgery, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
| | - Zhaoqiong Xing
- Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, Guangxi, China
| | - Mingwei Huang
- Department of Gastrointestinal Surgery, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
| | - Hongping Yu
- Department of Experimental Research, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
| | - Yuzhou Qin
- Department of Gastrointestinal Surgery, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
| | - Qinwen Jin
- Department of Gastrointestinal Surgery, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
| | - Zihan Zhou
- Department of Cancer Prevention and Control, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
| | - Jiansi Chen
- Department of Gastrointestinal Surgery, Guangxi Cancer Hospital and Guangxi Medical University Affiliated Cancer Hospital, Nanning, Guangxi, China
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Comparison of treatment strategies and survival of early-onset gastric cancer: a population-based study. Sci Rep 2022; 12:6288. [PMID: 35428811 PMCID: PMC9012810 DOI: 10.1038/s41598-022-10156-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 03/29/2022] [Indexed: 11/25/2022] Open
Abstract
Treatments for early-onset gastric cancer (EOGC) patients are rarely included in clinical trials, resulting in an unclear impact on survival. This study aimed to investigate the treatment patterns of EOGC patients and their impact on survival. Based on the Surveillance, Epidemiology, and End Results database, we conducted a retrospective analysis of 1639 EOGC patients (< 50 years) diagnosed between 2010 and 2018. Patients with larger tumours, distant metastasis, and AJCC TNM stage in IV were prone to receive nonsurgical treatment. Patients treated with surgery alone had a better prognosis than those receiving SROC or SCRT or nonsurgical treatment. However, analyses stratified by histological type, tumour size and TNM stage showed that patients did not benefit more from SROC and SCRT than from surgery alone. Similar results were observed in the stratified Cox regression risk analysis. Patients who received nonsurgical treatment had the highest risk of overall death [hazard ratio (HR) = 2.443, 95% confidence interval (CI) 1.865–3.200, P < 0.001]. This study indicated that additional radiotherapy, chemotherapy or chemoradiotherapy did not provide a coordinated survival benefit to EOGC patients.
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Charalampakis N, Tsakatikas S, Schizas D, Kykalos S, Tolia M, Fioretzaki R, Papageorgiou G, Katsaros I, Abdelhakeem AAF, Sewastjanow-Silva M, Rogers JE, Ajani JA. Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives. World J Gastrointest Oncol 2022; 14:181-202. [PMID: 35116110 PMCID: PMC8790425 DOI: 10.4251/wjgo.v14.i1.181] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 06/28/2021] [Accepted: 12/10/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric and gastroesophageal junction (GEJ) cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage, with an increasing incidence both in Asia and in Western countries. These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses. Accordingly, the understanding of phenotypic and genotypic correlations/classifications has been improved. Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone, with the incorporation of other treatment modalities, such as radiation and chemotherapy (including biologics). Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival. Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate, which is associated with improved long-term outcomes. Several studies have defined various chemotherapy regimens to accompany radiation (before and after surgery). Recently, addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval. Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results. The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers, highlight the remaining questions and present the current research effort addressing them.
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Affiliation(s)
- Nikolaos Charalampakis
- Department of Medical Oncology, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
| | - Sergios Tsakatikas
- Department of Medical Oncology, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
| | - Dimitrios Schizas
- TheFirst Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
| | - Stylianos Kykalos
- TheSecond Propedeutic Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens 11527, Greece
| | - Maria Tolia
- Department of Radiation Oncology, University Hospital of Crete, Heraklion 71110, Greece
| | - Rodanthi Fioretzaki
- Department of Medical Oncology, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
| | - Georgios Papageorgiou
- Department of Medical Oncology, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
| | - Ioannis Katsaros
- Department of General Surgery, Metaxa Cancer Hospital of Piraeus, Piraeus 18537, Greece
| | - Ahmed Adel Fouad Abdelhakeem
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Matheus Sewastjanow-Silva
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jane E Rogers
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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Abstract
The prognosis of advanced gastric cancer (AGC) is extremely poor, and the therapeutic effect of traditional palliative chemotherapy is far from satisfactory. To overcome this bottleneck, palliative surgery resection, perioperative chemotherapy combined with surgical resection, hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), radiation therapy, molecular-targeted therapy have been explored in AGC. Although considerable progress has been achieved, there is still no overwhelming therapeutic method. Due to the high heterogeneity of AGC, it is particularly vital to reshaped the paradigm of gastric cancer therapy according to the characteristics of clinical classifications and molecular subtypes.
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Affiliation(s)
- Tao Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yufang He
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Qinglei Zhong
- The First Clinical Medical School, Southern Medical University, Guangzhou, Guangdong, China
| | - Jiang Yu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xinhua Chen
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Vos EL, Carr RA, Hsu M, Nakauchi M, Nobel T, Russo A, Barbetta A, Tan KS, Tang L, Ilson D, Ku GY, Wu AJ, Janjigian YY, Yoon SS, Bains MS, Jones DR, Coit D, Molena D, Strong VE. Prognosis after neoadjuvant chemoradiation or chemotherapy for locally advanced gastro-oesophageal junctional adenocarcinoma. Br J Surg 2021; 108:1332-1340. [PMID: 34476473 PMCID: PMC8599637 DOI: 10.1093/bjs/znab228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 05/26/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Trials typically group cancers of the gastro-oesophageal junction (GOJ) with oesophageal or gastric cancer when studying neoadjuvant chemoradiation and perioperative chemotherapy, so the results may not be fully applicable to GOJ cancer. Because optimal neoadjuvant treatment for GOJ cancer remains controversial, outcomes with neoadjuvant chemoradiation versus chemotherapy for locally advanced GOJ adenocarcinoma were compared retrospectively. METHODS Data were collected from all patients who underwent neoadjuvant treatment followed by surgery for adenocarcinoma located at the GOJ at a single high-volume institution between 2002 and 2017. Postoperative major complications and mortality were compared between groups using Fisher's exact test. Overall survival (OS) and disease-free survival (DFS) were assessed by log rank test and multivariable Cox regression analyses. Cumulative incidence functions were used to estimate recurrence, and groups were compared using Gray's test. RESULTS Of 775 patients, 650 had neoadjuvant chemoradiation and 125 had chemotherapy. These groups were comparable in terms of clinical tumour and lymph node categories, although the chemoradiation group had greater proportions of white men, complete pathological response to chemotherapy, and smaller proportions of diffuse cancer, poor differentiation, and neurovascular invasion. Postoperative major complications (20.0 versus 17.6 per cent) and 30-day mortality (1.7 versus 1.6 per cent) were not significantly different between the chemoradiation and chemotherapy groups. After adjustment, type of therapy (chemoradiation versus chemotherapy) was not significantly associated with OS (hazard ratio (HR) 1.26, 95 per cent c.i. 0.96 to 1.67) or DFS (HR 1.27, 0.98 to 1.64). Type of recurrence (local, regional, or distant) did not differ after neoadjuvant chemoradiation versus chemotherapy. CONCLUSION In patients undergoing surgical resection for locally advanced adenocarcinoma of the GOJ, OS and DFS did not differ significantly between patients who had neoadjuvant chemoradiation compared with chemotherapy.
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Affiliation(s)
- E L Vos
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - R A Carr
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - M Hsu
- Department of Bioinformatics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - M Nakauchi
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - T Nobel
- Department of Surgery, Mount Sinai Health System, New York, New York, USA
| | - A Russo
- Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts, USA
| | - A Barbetta
- Department of Surgery, University of Southern California, Los Angeles, California, USA
| | - K S Tan
- Department of Bioinformatics, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - L Tang
- Department of Pathology, Experimental and Gastrointestinal Pathology Services, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - D Ilson
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - G Y Ku
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - A J Wu
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Y Y Janjigian
- Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - S S Yoon
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - M S Bains
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - D R Jones
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - D Coit
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - D Molena
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - V E Strong
- Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA
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10
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Lam AK, Bourke MJ, Chen R, Fiocca R, Fujishima F, Fujii S, Jansen M, Kumarasinghe P, Langer R, Law S, Meijer SL, Muldoon C, Novelli M, Shi C, Tang L, Nagtegaal ID. Dataset for the reporting of carcinoma of the esophagus in resection specimens: recommendations from the International Collaboration on Cancer Reporting. Hum Pathol 2021; 114:54-65. [PMID: 33992659 DOI: 10.1016/j.humpath.2021.05.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Accepted: 05/06/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES A standardized data set for esophageal carcinoma pathology reporting was developed based on the approach of the International Collaboration on Cancer Reporting (ICCR) for the purpose of improving cancer patient outcomes and international benchmarking in cancer management. MATERIALS AND METHODS The ICCR convened a multidisciplinary international expert panel to identify the best evidence-based clinical and pathological parameters for inclusion in the data set for esophageal carcinoma. The data set incorporated the current edition of the World Health Organization Classification of Tumours of the Digestive System, and Tumour-Node-Metastasis staging systems. RESULTS The scope of the data set encompassed resection specimens of the esophagus and esophagogastric junction with tumor epicenter ≤20 mm into the proximal stomach. Core reporting elements included information on neoadjuvant therapy, operative procedure used, tumor focality, tumor site, tumor dimensions, distance of tumor to resection margins, histological tumor type, presence and type of dysplasia, tumor grade, extent of invasion in the esophagus, lymphovascular invasion, response to neoadjuvant therapy, status of resection margin, ancillary studies, lymph node status, distant metastases, and pathological staging. Additional non-core elements considered useful to report included clinical information, specimen dimensions, macroscopic appearance of tumor, and coexistent pathology. CONCLUSIONS This is the first international peer-reviewed structured reporting data set for surgically resected specimens of the esophagus. The ICCR carcinoma of the esophagus data set is recommended for routine use globally and is a valuable tool to support standardized reporting, to benefit patient care by providing diagnostic and prognostic best-practice parameters.
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Affiliation(s)
- Alfred K Lam
- Pathology, School of Medicine and Dentistry, Gold Coast Campus, Griffith University, Gold Coast, Queensland, 4222, Australia; Pathology Queensland, Gold Coast University Hospital, Southport, Queensland, 4222, Australia; Faculty of Medicine, The University of Queensland, Herston, Queensland, 4006, Australia.
| | - Michael J Bourke
- Westmead Hospital, Department of Gastroenterology and Hepatology, Sydney, New South Wales, 2145, Australia; University of Sydney, Westmead Clinical School, Sydney, New South Wales, 2145, Australia.
| | - Renyin Chen
- Department of Pathology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450052, Henan Province, PR China.
| | - Roberto Fiocca
- Department of Pathology, University of Genova and IRCCS Policlinico San Martino, 16132, Genova, Italy.
| | - Fumiyoshi Fujishima
- Department of Pathology, Tohoku University Hospital, Aoba-ku, Sendai, 980-8574, Japan.
| | - Satoshi Fujii
- Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan; Department of Pathology and Clinical Laboratories, National Cancer Centre Hospital East, Kashiwa, 6-5-1, Japan.
| | - Marnix Jansen
- University College London (UCL) Cancer Institute, London, United Kingdom; University College London Hospitals NHS Trust, London, WC1E 6DD, United Kingdom.
| | - Priyanthi Kumarasinghe
- PathWest Laboratory Medicine, PathWest QEII Medical Centre, Perth, 6009, Western Australia, Australia.
| | - Rupert Langer
- Institute of Pathology, University of Bern, 3012 Bern, Switzerland.
| | - Simon Law
- Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
| | - Sybren L Meijer
- Department of Pathology, Amsterdam UMC, University of Amsterdam, Amsterdam, 1105, AZ, the Netherlands.
| | - Cian Muldoon
- Histopathology Department, St James's Hospital, Dublin, D08 NHY1, Ireland.
| | - Marco Novelli
- Research Department of Pathology, University College London Medical School, London, WC1E 6DD, United Kingdom.
| | - Chanjuan Shi
- Department of Pathology, Duke University School of Medicine, Durham, NC, 27708, United States.
| | - Laura Tang
- Department of Pharmacy, Memorial Sloan Kettering Cancer Centre, New York City, NY, 10065, United States.
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Centre, Nijmegen, 6500, the Netherlands.
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11
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Zhai J, Wu J, Wang Y, Fan R, Xie G, Wu F, He Y, Qian S, Tan A, Yao X, He M, Shen L. Prediction of Sensitivity and Efficacy of Clinical Chemotherapy Using Larval Zebrafish Patient-Derived Xenografts of Gastric Cancer. Front Cell Dev Biol 2021; 9:680491. [PMID: 34164399 PMCID: PMC8215369 DOI: 10.3389/fcell.2021.680491] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 04/26/2021] [Indexed: 12/27/2022] Open
Abstract
Background Perioperative chemotherapy has been accepted as one of the most common approaches for locally advanced gastric cancer. However, the efficacy of chemotherapy varies among patients, and there is no effective method to predict the chemotherapy efficacy currently. We previously established the first larval zebrafish patient-derived xenografts (zPDXs) of gastric cancer as a platform for the translational research and personalized treatment. The objective of this study was to investigate the feasibility of screening individualized chemotherapeutics using the zPDXs. Methods We further optimized this zPDXs platform including administration route, drug dosing, and rhythm to develop a stable and reliable protocol for chemotherapeutics screening. Using the novel platform, we investigated the chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for gastric cancer patients. Results We showed that the engrafted zebrafish retained the original prominent cell components of the corresponding human tumor tissues, and we successfully obtained the results of chemosensitivity of 5-fluorouracil, cisplatin, docetaxel, and doxorubicin for 28 patients with locally advanced gastric cancer. These patients underwent radical gastrectomy for curative intent and 27 cases received postoperative adjuvant chemotherapy. We revealed that the chemosensitivity obtained from zPDXs was consistent with the clinical responses in these patients (P = 0.029). More importantly, the responder drug(s) from zPDXs used or not was the only risk factor for early-stage recurrence in these 27 patients (P = 0.003). Conclusion Our study with the largest sample size so far suggests that larval zPDXs help to predict the chemotherapeutics response and to achieve precise chemotherapy for gastric cancer.
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Affiliation(s)
- Jing Zhai
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiaqi Wu
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Yaohui Wang
- Department of Pathology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Ruoyue Fan
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Guiping Xie
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Fangfang Wu
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Yani He
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Sitong Qian
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Aimin Tan
- Nanjing Amory Biotech Co. Ltd., Nanjing, China
| | - Xuequan Yao
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Mingfang He
- Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, China
| | - Lizong Shen
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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12
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Stark AP, Blum MM, Chiang YJ, Das P, Minsky BD, Estrella JS, Ajani JA, Badgwell BD, Mansfield P, Ikoma N. Preoperative Therapy Regimen Influences the Incidence and Implication of Nodal Downstaging in Patients with Gastric Cancer. J Gastric Cancer 2020; 20:313-327. [PMID: 33024587 PMCID: PMC7521984 DOI: 10.5230/jgc.2020.20.e29] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/08/2020] [Accepted: 09/01/2020] [Indexed: 12/19/2022] Open
Abstract
Purpose Nodal downstaging after preoperative therapy for gastric cancer has been shown to impart excellent prognosis, but this has not been validated in a national cohort. The role of neoadjuvant chemoradiation (NACR) in nodal downstaging remains unclear when compared with that of neoadjuvant chemotherapy alone (NAC). Furthermore, it is unknown whether the prognostic implications of nodal downstaging differ by preoperative regimen. Materials and Methods Using the National Cancer Database, overall survival (OS) duration was compared among natural N0 (cN0/ypN0), downstaged N0 (cN+/ypN0), and node-positive (ypN+) gastric cancer patients treated with NACR or NAC. Factors associated with nodal downstaging were examined in a propensity score-matched cohort of cN+ patients, matched 1:1 by receipt of NACR or NAC. Results Of 7,426 patients (natural N0 [n=1,858, 25.4%], downstaged N0 [n=1,813, 24.4%], node-positive [n=3,755, 50.4%]), 58.2% received NACR, and 41.9% received NAC. The median OS durations of downstaged N0 (5.1 years) and natural N0 (5.6 years) patients were similar to one another and longer than that of node-positive patients (2.1 years) (P<0.001). In the matched cohort of cN+ patients, more recent diagnosis (2010–2015 vs. 2004–2009) (odds ratio [OR], 2.57; P<0.001) and NACR (OR, 2.02; P<0.001) were independently associated with nodal downstaging. The 5-year OS rate of downstaged N0 patients was significantly lower after NACR (46.4%) than after NAC (57.7%) (P=0.003). Conclusions Downstaged N0 patients have the same prognosis as natural N0 patients. Nodal downstaging occurred more frequently after NACR; however, the survival benefit of nodal downstaging after NACR may be less than that when such is achieved by NAC.
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Affiliation(s)
- Alexander P Stark
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mariela M Blum
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yi-Ju Chiang
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Prajnan Das
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeannelyn S Estrella
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian D Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul Mansfield
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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