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Consensus on the clinical diagnosis and treatment of grade 3 pancreatic neuroendocrine tumors

胰腺病学杂志(英文) 2024年第2期07卷 97-105页

作者： Chen Jie Wu Wenming Bai Chunmei chi yihebali Huo Li Jiang Liming Ji Yuan Luo Jie Li Jie Li Jingnan Lou Wenhui Shao Chenghao Shen Lin Wang Feng Wang Yu Xue Ling Xu Jin Yuan Chunhui Yu Xianjun Yin Xiaoyu Zhao Hong Zhu Xiongzeng Zhao Yupei Centre for Neuroendocrine Tumors Fudan University Shanghai Cancer Center Shanghai China Department of General Surgery State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science and Peking Union Medical College Beijing China Department of Medical Oncology Peking Union Medical College Hospital Chinese Academy of Medical Science &amp Peking Union Medical College Beijing China Department of Medical Oncology National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Nuclear Medicine State Key Laboratory of Complex Severe and Rare Diseases Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing China Department of Diagnostic Radiology National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Pathology Zhongshan Hospital Fudan University Shanghai China Department of Pathology China-Japan Friendship Hospital Beijing China Department of Gastroenterological Oncology Beijing Cancer Hospital Peking University Cancer Hospital &amp Institute Beijing China Department of Gastroenterology Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing China Department of Pancreatic Surgery Zhongshan Hospital Fudan University Shanghai China Department of Pancreatic-Biliary Surgery Second Affiliated Hospital of Naval Medical University Shanghai China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Peking University Cancer Hospital &amp Department of Nuclear Medicine Nanjing First Hospital Nanjing Medical University Nanjing China Depar

The World Health Organization (WHO) 2017 classifications for neuroendocrine neoplasms (NENs) subdivided grade 3 pancreatic neuroendocrine neoplasms (pNENs) into G3 well-differentiated pancreatic neuroendocrine tumors (G3 pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs), according to the mitotic count, Ki-67 index, and cell differentiation. As a new category, G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice. Therefore, the chinese Pancreatic Surgery Association, chinese Society of Surgery, chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

关键词： Clinical diagnosis Grade 3 Pancreatic neuroendocrine tumors Treatment

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PhaseⅠdose-finding study of sorafenib with FOLFOX4 as firstline treatment in patients with unresectable locally advanced or metastatic gastric cancer

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chinese Journal of Cancer Research 2015年第3期27卷 239-246页

作者： yihebali chi Jianliang Yang Sheng Yang Yongkun Sun Bo Jia Yuankai Shi Department of Medical Oncology Cancer HospitalChinese Academy of Medical Sciences & Peking Union Medical College National Center for Anticancer Drugs Clinical Study Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs

Objective： To determine the maximum tolerated dose（MTD）, dose-limiting toxicity（DLT） and efficacy of sorafenib in combination with FOLFOX4（oxaliplatin/leucovorin（LV）/5-fluorouracil） as first-line treatment for advanced gastric cancer, we performed a phase I dose-finding study in nine evaluable patients with unresectable locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Methods： According to modified Fibonacci method, the design of this study was to guide elevation of the sorafenib dosage to the next level（from 200 mg twice daily to 400 mg twice daily and then, if tolerated, 600 mg twice daily）. If the patient achieved complete response（CR）, partial response（PR） or stable disease（SD） after eight cycles of treatment, combination chemotherapy was scheduled to be discontinued and sorafenib monotherapy continued at the original dose until either disease progression or unacceptable toxicity. Results： In sorafenib 200 mg twice daily group, DLT was observed in 1 of 6 patients, and in 400 mg twice daily group, it was observed in 2 of 3 patients. Seven of 9（77.8%） evaluable patients achieved PR, with a median overall survival（OS） of 11.8 [95% confidence interval（CI）： 8.9-14.7] months. Common adverse effects include hand-foot syndrome, leukopenia, neutropenia, anorexia, and ***： Twice-daily dosing of sorafenib 200 mg in combination with FOLFOX4 was proven effective and safe for the treatment of advanced gastric cancer, and could be an appropriate dosage for subsequent phase II clinical studies.

关键词： Sorafenib gastric cancer FOLFOX4

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Characteristics and long-term prognosis of patients with rectal neuroendocrine tumors

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World Journal of Gastroenterology 2014年第43期20卷 16252-16257页

作者： yihebali chi Feng Du Hong Zhao Jin-Wan Wang Jian-Qiang Cai Cancer Institute and Hospital Chinese Academy of Medical Sciences

AIM: To analyze the clinicopathologic characteristics and prognostic factors of rectal neuroendocrine tumors.

关键词： Rectal neuroendocrine tumors Clinical characteristics Prognostic factors

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A phase II trial of oxaliplatin plus S-1 as a first-fine chemotherapy for patients with advanced gastric cancer

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chinese Medical Journal 2013年第18期 3470-3474页

作者： YANG Lin SONG Yan ZHOU Ai-ping QIN Qiong chi yihebali HUANG Jing WANG Jin-wan Department of Medical Oncology Cancer Hospital and Institute Chinese Academy of Medical Sciences Beijing 100021 China

Background Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer. We conducted a Phase II trial to determine the efficacy and safety of S-1 plus oxaliplatin （SOX regimen） as first-line chemotherapy for patients with unresectable locally advanced or metastatic gastric cancer. Methods Eligible patients had measurable lesions and no previous history of chemotherapy （except adjuvant chemotherapy）. Oxaliplatin was administered intravenously at a dose of 130 mg/m2 on day 1. S-1 was administered orally in doses of 80, 100, or 120 mg/d according to body surface areas of 〈1.25 m2, 1.25-1.5 m2, or 〉1.5 m2 respectively; the total dose was divided into two daily doses on days 1-14. Treatments were repeated every 3 weeks until disease progression or intolerable toxicity occurred. Results Forty-three patients were enrolled in the study. All were assessable for efficacy and adverse events. The objective response and disease control rates were 55.8% and 76.7% respectively. The median follow-up time was 16.5 months. The median progression-free survival time was 7 months （95% CI, 5.8-8.2 months） and the median overall survival time was 16.5 months （95% CI, 9.7-23.3 months）. The one-year survival rate was 54.2%. Major adverse reactions were grade 3/4 neutropenia （9.3%） and thrombocytopenia （20.9%）. Conclusion The SOX regimen with oxaliplatin at a dose of 130 mg/m2 was found to be effective and safe as a first-line chemotherapy in chinese patients with advanced gastric cancer.

关键词： stomach neoplasms drug therapy oxaliplatin S-1

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Clinicopathological Characteristics and Prognosis of Colorectal Cancer in chinese Adolescent Patients

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chinese Medical Journal 2015年第23期128卷 3149-3152页

作者： Feng Du Su-Sheng Shi Yong-Kun Sun Jin-Wan Wang yihebali chi Department of Medical Oncology Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 China Department of Pathology Cancer Hospital Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100021 China

Background： Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair （MMR） status may relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis. Methods： The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method. Results： The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type （7/19）. Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor （P = 0.02）. Conclusions： Colorectal cancer in chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage Ⅲ/Ⅳdisease with signet ring cell carcinoma. The prognosis was relatively poor.

关键词： Adolescence Colorectal Cancer Prognosis

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Phase II clinical study on the modified DCF regimen for treatment of advanced gastric carcinoma

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chinese Medical Journal 2011年第19期124卷 2997-3002页

作者： yihebali chi REN Jian-hong YANG Lin CUI Cheng-xu LI Jun-ling WANG Jin-wan Department of Medical Oncology Cancer Hospital ＆ InstituteChinese Academy of Medical Sciences Beijing 100021 China

Background A phase Ⅲ trial involving docetaxel, cisplatin, and fluorouracil （DCF） in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel （D） and cis-platinum （CDDP）, and administered 5-fluorouracil （5-FU） via a continuous intravenous （CIV） *** Chemotherapy-naive patients with gastric adenocarcinomas received D （60 mg/m2 1 hour on day 1）, CDDP （30 mg/m2on days 1 and 2）, and 5-FU （1500 mg·m-2·24 h-1 CIV on days 1 and 8 every 3 weeks）. The primary endpoint was the response *** Fourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission （CR）, 71% partial remission （PR）, 14% stable disease （NC/SD）, and 7.1% progressive disease （PD）. The median survival time was 13 months. Nine patients （64%） had grade Ⅲ-Ⅳ neutropenia, and 4 patients （29%） had grade Ⅳ neutropenia, among whom 1 had grade Ⅳ neutropenia with grade Ⅲ nausea and *** The modified DCF regimen is highly active and has a favorable toxicity profile in chinese patients with gastric cancer.

关键词： gastric cancer modified DCF regimen docetaxel cis-platinum 5-fluorouracil

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A phase Ⅱ trial of oxaliplatin plus S-1 as a first-line chemotherapy for patients with advanced gastric cancer

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中华医学杂志(英文版) 2013年第18期126卷 3470-3474页

作者： YANG Lin SONG Yan ZHOU Ai-ping QIN Qiong chi yihebali HUANG Jing WANG Jin-wan Department of Medical Oncology Cancer Hospital and InstituteChinese Academy of Medical Sciences

Background Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric *** conducted a Phase II trial to determine the efficacy and safety of S-1 plus oxaliplatin（SOX regimen）as first-line chemotherapy for patients with unresectable locally advanced or metastatic gastric *** Eligible patients had measurable lesions and no previous history of chemotherapy（except adjuvant chemotherapy）.Oxaliplatin was administered intravenously at a dose of 130 mg/m2on day 1.S-1 was administered orally in doses of 80,100,or 120 mg/d according to body surface areas of1.5 m2respectively;the total dose was divided into two daily doses on days *** were repeated every 3 weeks until disease progression or intolerable toxicity *** Forty-three patients were enrolled in the *** were assessable for efficacy and adverse *** objective response and disease control rates were 55.8%and 76.7%*** median follow-up time was 16.5 *** median progression-free survival time was 7 months（95%CI,5.8-8.2 months）and the median overall survival time was16.5 months（95%CI,9.7-23.3 months）.The one-year survival rate was 54.2%.Major adverse reactions were grade 3/4neutropenia（9.3%）and thrombocytopenia（20.9%）.Conclusion The SOX regimen with oxaliplatin at a dose of 130 mg/m2was found to be effective and safe as a first-line chemotherapy in chinese patients with advanced gastric cancer.

关键词： stomach neoplasms drug therapy oxaliplatin S-1

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Efficacy and toxicity of capecitabine combined with intensitymodulated radiotherapy after D1/D2 lymph node dissection in patients with gastric cancer

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World Journal of Gastrointestinal Oncology 2021年第10期13卷 1532-1543页

作者： Xin Wang Wei-Hu Wang Shu-Lian Wang Yong-Wen Song Yue-Ping Liu Yuan Tang Ning Li Wen-Yang Liu Hui Fang Ye-Xiong Li Dong-Bing Zhao yihebali chi Lin Yang Jing Jin Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiation Oncology Peking University Cancer Hospital and InstituteBeijing 100001China Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhen 518116Guangdong ProvinceChina Department of Pancreatic and Gastric Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND Adjuvant chemoradiotherapy(ACRT)with oral capecitabine and intensitymodulated radiotherapy(IMRT)were well tolerated in a phase I study in patients who had undergone partial or total gastrectomy for locally advanced gastric cancer(GC).This phase II study aimed to further determine the efficacy and toxicity of this combination after radical resection and D1/D2 lymph node dissection(LND)for patients with locally advanced *** To further determine the efficacy and toxicity of this combination after radical resection and D1/D2 LND for patients with locally advanced *** Forty patients(median age,53 years;range,24-71 years)with pathologically confirmed adenocarcinoma who underwent D1/D2 LND were included in this *** patients received ACRT comprising IMRT(total irradiation dose:45 Gy delivered in daily 1.8-Gy fractions on 5 d a week over 5 wk)and capecitabine chemotherapy(dose:800 mg/m²twice daily throughout the duration of radiotherapy).The primary study endpoint was disease-free survival(DFS),and the secondary endpoints were overall survival(OS),toxic effects,and treatment *** The 3-year DFS and OS were 66.2%and 75%,*** median time to recurrence was 19.5 mo(range,6.1-68 mo).Peritoneal implantation(n=10)was the most common recurrence pattern,and the lung was the most common site of extra-abdominal metastases(n=5).Nine patients developed grade 3 or 4 toxicities during *** patients discontinued ACRT,while eleven underwent ACRT without receiving the entire course of *** were no treatmentrelated *** The ACRT protocol described herein showed acceptable safety and efficacy for patients with locally advanced GC who received radical gastrectomy and D1/2 LND.

关键词： Gastric cancer Radiotherapy Chemoradiotherapy Clinical trial Phase II

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Down-staging depth score could be a survival predictor for locally advanced gastric cancer patients after preoperative chemoradiotherapy

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chinese Journal of Cancer Research 2021年第4期33卷 447-456页

作者： Ning Li Xin Wang Yuan Tang Dongbin Zhao yihebali chi Lin Yang Liming Jiang Jun Jiang Jinming Shi Wenyang Liu Hua Ren Hui Fang Yu Tang Bo Chen Ningning Lu Hao Jing Shunan Qi Shulian Wang Yueping Liu Yongwen Song Yexiong Li Jing Jin State Key Laboratory of Molecular Oncology Department of Radiation OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100021China Department of Abdominal Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized *** examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative ***:From April 2012 to April 2019,95 patients with locally advanced gastric cancer who received preoperative concurrent CRT and who were enrolled in three prospective studies were *** patients were stage T_(3/4) N_(+).Local control,distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)were *** factors related to long-term prognosis were analyzed using univariate and multivariate *** down-staging depth score(DDS),which is a novel method of evaluating CRT response,was used to predict long-term ***:The median follow-up period for survivors was 30 *** area under the curve(AUC)of the receiver operating characteristic(ROC)curve predicted by the DDS was 0.728,which was better than the pathological complete response(pCR),histological response and *** curve analysis further affirmed that DDS had the largest net *** DDS cut-off value was *** and ypN0 were associated with OS(P=0.026 and 0.049).Surgery and DDS are correlated with DMFS,DFS and OS(surgery:P=0.001,<0.001 and<0.001,respectively;and DDS:P=0.009,0.013 and 0.032,respectively).Multivariate analysis showed that DDS was an independent prognostic factor of DFS(P=0.021).Conclusions:DDS is a simple,short-term indicator that was a better surrogate endpoint than pCR,histological response and ypN0 for DFS.

关键词： Gastric cancer preoperative chemoradiotherapy prediction long-term outcomes

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22例妊娠期胃癌的临床特点及预后分析

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中华肿瘤杂志 2018年第8期40卷 631-635页

作者：姜志超依荷巴丽·迟国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院内科 100021

目的总结妊娠期胃癌的临床病理特点及预后。方法2001—2016年中国医学科学院肿瘤医院收治的妊娠期胃癌患者10例和在中国知网、万方数据电子期刊数据库、维普电子期刊全文数据库检索到的同期妊娠期胃癌患者12例，收集患者的临床特征、病... 详细信息

目的总结妊娠期胃癌的临床病理特点及预后。方法2001—2016年中国医学科学院肿瘤医院收治的妊娠期胃癌患者10例和在中国知网、万方数据电子期刊数据库、维普电子期刊全文数据库检索到的同期妊娠期胃癌患者12例，收集患者的临床特征、病理学特征、TNM分期、治疗策略、胎儿及患者的预后等信息。结果22例患者临床表现主要为恶心呕吐（14例）、黑便（8例）、腹胀（7例）和腹痛（6例）。并发消化道出血9例，肠梗阻3例，胃穿孔2例。低分化腺癌14例，印戒细胞癌7例。分期为Ⅰ期1例，Ⅳ期17例。腹膜转移（7例）和卵巢转移（5例）最为常见。3例于妊娠早期确诊的患者行人工流产手术。5例妊娠中期患者中，3例行引产手术。3例妊娠晚期患者均于确诊后立即行剖宫产手术。6例行胃癌根治性手术，5例行姑息手术。围手术期化疗方案主要为以奥沙利铂及氟尿嘧啶为主的2药或3药方案。晚期患者的一线化疗方案以铂类和氟尿嘧啶类的联合方案为主，二线化疗方案以含伊立替康或雷替曲塞的方案为主。22例妊娠期胃癌患者的1年生存率为23.1%，2年生存率为15.4%。3例接受R0切除的患者生存时间超过18个月。结论组织分化差和分期晚是妊娠期胃癌患者预后差的主要原因。目前妊娠期胃癌尚缺乏有效治疗策略。由于分期晚，多数患者无法手术切除肿瘤。晚期患者的一线化疗方案以铂类和氟尿嘧啶类的联合方案为主，二线化疗方案以含伊立替康或雷替曲塞的方案为主。

关键词：胃肿瘤妊娠临床特征预后

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