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 fo...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 nausea.Conclusions： 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.展开更多
胃癌是最常见的恶性肿瘤之一,部分病例由于诊断较晚和治疗不佳,患者的整体生存期较差。近几年,嵌合抗原受体修饰T细胞(chimeric antigen receptor T cells,CAR-T)疗法在肿瘤治疗研究领域受到相当大的关注,且已在血液系统肿瘤中发挥了重...胃癌是最常见的恶性肿瘤之一,部分病例由于诊断较晚和治疗不佳,患者的整体生存期较差。近几年,嵌合抗原受体修饰T细胞(chimeric antigen receptor T cells,CAR-T)疗法在肿瘤治疗研究领域受到相当大的关注,且已在血液系统肿瘤中发挥了重要作用,但在实体肿瘤因受到靶点特异性,肿瘤微环境等因素影响而作用受限。尽管如此,各种临床前和临床实验已证实CAR-T细胞免疫治疗是胃癌一种有前景的治疗方法,并具有有别于其他实体瘤的优势,但是仍面临诸多挑战。本文将系统介绍CAR-T疗法在胃癌中的最新研究进展。展开更多
Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer...Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT.Methods: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 included.All patients were stage T_(3/4) N_(+).Local control,distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)were evaluated.Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses.The down-staging depth score(DDS),which is a novel method of evaluating CRT response,was used to predict long-term outcomes.Results:The median follow-up period for survivors was 30 months.The 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 ypN0.Decision curve analysis further affirmed that DDS had the largest net benefit.The DDS cut-off value was 4.pCR 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.展开更多
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 ...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 GC.AIM To further determine the efficacy and toxicity of this combination after radical resection and D1/D2 LND for patients with locally advanced GC.METHODS Forty patients(median age,53 years;range,24-71 years)with pathologically confirmed adenocarcinoma who underwent D1/D2 LND were included in this study.The 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 compliance.RESULTS The 3-year DFS and OS were 66.2%and 75%,respectively.The 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 ACRT.Two patients discontinued ACRT,while eleven underwent ACRT without receiving the entire course of capecitabine.There were no treatmentrelated deaths.CONCLUSION The ACRT protocol described herein showed acceptable safety and efficacy for patients with locally advanced GC who received radical gastrectomy and D1/2 LND.展开更多
Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association ...Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial(NCT02589821)and obtained contrast-enhanced computed tomography(CECT)images.Qualitative and quantitative parameters including hepatic tumor margins,lesion volumes,enhancement pattern,localization types,and enhancement ratios were evaluated.The progression-free survival(PFS)and hazard ratio(HR)were calculated using Cox’s proportional hazard model.Efficacy was analyzed by logistic-regression models.Results:Among 152 patients who had baseline CECT assessments and were included in this analysis,the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters.In the multivariable analysis of patients receiving surufatinib(N=100),those with higher arterial phase standardized enhancement ratio-peri-lesion(ASER-peri)exhibited longer PFS[HR=0.039;95%confidence interval(95%CI):0.003−0.483;P=0.012].Furthermore,patients with a high enhancement pattern experienced an improvement in the objective response ratio[31.3%vs.14.7%,odds ratio(OR)=3.488;95%CI:1.024−11.875;P=0.046],and well-defined tumor margins were associated with a higher disease control rate(DCR)(89.3%vs.68.2%,OR=4.535;95%CI:1.285−16.011;P=0.019)compared to poorlydefined margins.Conclusions:These pre-treatment radiological features,namely high ASER-peri,high enhancement pattern,and well-defined tumor margins,have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.展开更多
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 ...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.展开更多
Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases.However,a lack of biological,molecular,and genomic information and an absence of data from rigorous trials limit t...Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases.However,a lack of biological,molecular,and genomic information and an absence of data from rigorous trials limit the validity of these strategies.This review presents the viewpoints from an international conference consisting of several expert working groups.The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature,evaluating the evidence on which management decisions were based,developing internationally acceptable recommendations for clinical practice,and making recommendations for clinical and research endeavors.The review for each question will be followed by recommendations from the panel.展开更多
Pancreatic neuroendocrine neoplasms(pNENs)are highly heterogeneous,and the management of pNENs patients can be intractable.To address this challenge,an expert committee was established on behalf of the Chinese Pancrea...Pancreatic neuroendocrine neoplasms(pNENs)are highly heterogeneous,and the management of pNENs patients can be intractable.To address this challenge,an expert committee was established on behalf of the Chinese Pancreatic Surgery Association,which consisted of surgical oncologists,gastroenterologists,medical oncologists,endocrinologists,radiologists,pathologists,and nuclear medicine specialists.By reviewing the important issues regarding the diagnosis and treatment of pNENs,the committee concluded evidence-based statements and recommendations in this article,in order to further improve the management of pNENs patients in China.展开更多
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 pNE...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.展开更多
基金supported by the Chinese National Major Project for New Drug Innovation(2008ZX09312,2012ZX09303012)Bayer Health Care Ltd.for partial financial support and Content Ed Net(Shanghai)Co.,Ltd.for editorial support
文摘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 nausea.Conclusions： 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.
文摘胃癌是最常见的恶性肿瘤之一,部分病例由于诊断较晚和治疗不佳,患者的整体生存期较差。近几年,嵌合抗原受体修饰T细胞(chimeric antigen receptor T cells,CAR-T)疗法在肿瘤治疗研究领域受到相当大的关注,且已在血液系统肿瘤中发挥了重要作用,但在实体肿瘤因受到靶点特异性,肿瘤微环境等因素影响而作用受限。尽管如此,各种临床前和临床实验已证实CAR-T细胞免疫治疗是胃癌一种有前景的治疗方法,并具有有别于其他实体瘤的优势,但是仍面临诸多挑战。本文将系统介绍CAR-T疗法在胃癌中的最新研究进展。
基金supported by grants from the National Natural Science Foundation of China(No.81773241 and No.81871509)。
文摘Objective:The predictive effect of preoperative chemoradiotherapy(CRT)is low and difficult in guiding individualized treatment.We examined a surrogate endpoint for long-term outcomes in locally advanced gastric cancer patients after preoperative CRT.Methods: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 included.All patients were stage T_(3/4) N_(+).Local control,distant metastasis-free survival(DMFS),disease-free survival(DFS)and overall survival(OS)were evaluated.Clinicopathological factors related to long-term prognosis were analyzed using univariate and multivariate analyses.The down-staging depth score(DDS),which is a novel method of evaluating CRT response,was used to predict long-term outcomes.Results:The median follow-up period for survivors was 30 months.The 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 ypN0.Decision curve analysis further affirmed that DDS had the largest net benefit.The DDS cut-off value was 4.pCR 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.
基金the Independent Ethics Committees of Cancer Institute and Hospital,Chinese Academy of Medical Sciences(Approved No.11-72/507).
文摘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 GC.AIM To further determine the efficacy and toxicity of this combination after radical resection and D1/D2 LND for patients with locally advanced GC.METHODS Forty patients(median age,53 years;range,24-71 years)with pathologically confirmed adenocarcinoma who underwent D1/D2 LND were included in this study.The 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 compliance.RESULTS The 3-year DFS and OS were 66.2%and 75%,respectively.The 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 ACRT.Two patients discontinued ACRT,while eleven underwent ACRT without receiving the entire course of capecitabine.There were no treatmentrelated deaths.CONCLUSION The ACRT protocol described herein showed acceptable safety and efficacy for patients with locally advanced GC who received radical gastrectomy and D1/2 LND.
文摘Objective:Currently,pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases(PNELM)receiving surufatinib treatment was unsatisfying.Our objective was to examine the association between radiological characteristics and efficacy/prognosis.Methods:We enrolled patients with liver metastases in the phase III,SANET-p trial(NCT02589821)and obtained contrast-enhanced computed tomography(CECT)images.Qualitative and quantitative parameters including hepatic tumor margins,lesion volumes,enhancement pattern,localization types,and enhancement ratios were evaluated.The progression-free survival(PFS)and hazard ratio(HR)were calculated using Cox’s proportional hazard model.Efficacy was analyzed by logistic-regression models.Results:Among 152 patients who had baseline CECT assessments and were included in this analysis,the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters.In the multivariable analysis of patients receiving surufatinib(N=100),those with higher arterial phase standardized enhancement ratio-peri-lesion(ASER-peri)exhibited longer PFS[HR=0.039;95%confidence interval(95%CI):0.003−0.483;P=0.012].Furthermore,patients with a high enhancement pattern experienced an improvement in the objective response ratio[31.3%vs.14.7%,odds ratio(OR)=3.488;95%CI:1.024−11.875;P=0.046],and well-defined tumor margins were associated with a higher disease control rate(DCR)(89.3%vs.68.2%,OR=4.535;95%CI:1.285−16.011;P=0.019)compared to poorlydefined margins.Conclusions:These pre-treatment radiological features,namely high ASER-peri,high enhancement pattern,and well-defined tumor margins,have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib.
文摘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.
基金supported by the National Natural Science Foundation of China(Grant number,82141127).
文摘Many management strategies are available for pancreatic neuroendocrine neoplasms with liver metastases.However,a lack of biological,molecular,and genomic information and an absence of data from rigorous trials limit the validity of these strategies.This review presents the viewpoints from an international conference consisting of several expert working groups.The working groups reviewed a series of questions of particular interest to clinicians taking care of patients with pancreatic neuroendocrine neoplasms with liver metastases by reviewing the existing management strategies and literature,evaluating the evidence on which management decisions were based,developing internationally acceptable recommendations for clinical practice,and making recommendations for clinical and research endeavors.The review for each question will be followed by recommendations from the panel.
基金supported by the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(CIFMS)2017-I2M-1-001.
文摘Pancreatic neuroendocrine neoplasms(pNENs)are highly heterogeneous,and the management of pNENs patients can be intractable.To address this challenge,an expert committee was established on behalf of the Chinese Pancreatic Surgery Association,which consisted of surgical oncologists,gastroenterologists,medical oncologists,endocrinologists,radiologists,pathologists,and nuclear medicine specialists.By reviewing the important issues regarding the diagnosis and treatment of pNENs,the committee concluded evidence-based statements and recommendations in this article,in order to further improve the management of pNENs patients in China.
基金supported by the National Natural Science Foundation of China(Grant No.82141104)National Natural Science Foundation of China(Grant No.82141102)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(Grant No.2021-I2M-1-002).
文摘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.
