BACKGROUND It is unclear whether treatment delay affects the clinical outcomes of chemotherapy in advanced gastric cancer(A-GC).AIM To assess whether treatment delay affects the clinical outcomes of chemotherapy in A-...BACKGROUND It is unclear whether treatment delay affects the clinical outcomes of chemotherapy in advanced gastric cancer(A-GC).AIM To assess whether treatment delay affects the clinical outcomes of chemotherapy in A-GC.METHODS This single-center retrospective study examined consecutive patients with A-GC between April 2012 and July 2018. In total, 110 patients with stage Ⅳ A-GC who underwent chemotherapy were enrolled. We defined the wait time(WT) as the interval between diagnosis and chemotherapy initiation. We evaluated the influence of WT on overall survival(OS).RESULTS The mean OS was 303 d. The median WT was 17 d. We divided the patients into early and elective WT groups, with a 2-wk cutoff point. There were 46 and 64 patients in the early and elective WT groups, respectively. Compared with the elective WT group, the early WT group had significantly lower albumin(Alb)levels and higher neutrophil/lymphocyte ratios and C-reactive protein(CRP)levels but not a lower performance status. The elective WT group underwent more combination chemotherapy than did the early WT group. OS was different between the two groups(230 d vs 340 d, respectively). Multivariate analysis revealed that higher CRP levels, lower Alb levels and monotherapy were significantly related to a poor prognosis. To minimize potential selection bias,patients in the elective WT group were 1:1 propensity score matched with patients in the early WT group; no significant difference in OS was found(303 d vs 311 d, respectively, log-rank P = 0.9832).CONCLUSION A longer WT in patients with A-GC does not appear to be associated with a worse prognosis.展开更多
AIM To evaluate whether the neoadjuvant chemotherapy(NAc T)-surgery interval time significantly impacts the pathological complete response(pc R) rate and longterm survival.METHODS One hundred and seventy-six patients ...AIM To evaluate whether the neoadjuvant chemotherapy(NAc T)-surgery interval time significantly impacts the pathological complete response(pc R) rate and longterm survival.METHODS One hundred and seventy-six patients with gastric cancer undergoing NAc T and a planned gastrectomy at the chinese p LA General hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NAc T-surgery interval time(< 4 wk, 4-6 wk, and > 6 wk) on pc R rate and overall survival(OS).RESULTS The NAc T-surgery interval time and clinician T stage were independent predictors of pc R. The interval time > 6 wk was associated with a 74% higher odds of pc R as compared with an interval time of 4-6 wk(p = 0.044), while the odds ratio(OR) of clinical T3 vs clinical T4 stage for pc R was 2.90(95%c I: 1.04-8.01, p = 0.041). In cox regression analysis of long-term survival, postneoadjuvant therapy pathological N(yp N) stage significantly impacted OS(N0 vs N3: h R = 0.16, 95%c I: 0.37-0.70, p = 0.015; N1 vs N3: h R = 0.14, 95%c I: 0.02-0.81, p = 0.029) and disease-free survival(DFS)(N0 vs N3: h R = 0.11, 95%c I: 0.24-0.52, p = 0.005; N1 vs N3: h R = 0.17, 95%c I: 0.02-0.71, p = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12(95%c I: 0.33-0.42, p = 0.001) for OS, and 0.13(95%c I: 0.36-0.44, p = 0.001) for DFS.CONCLUSION The NAc T-surgery interval time is associated with pc R but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pc R.展开更多
With the increase in average life expectancy,the rate of occurrence of gastric cancer in elderly patients is also rising.While many clinical trials have been conducted to examine the effect of chemotherapy treatment o...With the increase in average life expectancy,the rate of occurrence of gastric cancer in elderly patients is also rising.While many clinical trials have been conducted to examine the effect of chemotherapy treatment on gastric cancer,age limits for eligible subjects have prevented the establishment of standards for chemotherapy in elderly patients with gastric cancer.As of March 2009,evidence-based standard chemotherapy regimens were established.In the Western world,debates centered on the ECF(Epirubicin/cisplatin/5FU) or DCF(Docetaxel/cisplatin/5-FU) regimens based on the phase □ randomized controlled trial at the Royal Marsden Hospital(RMH) or the V325 study,respectively.The JCOG9912 and SPIRITS trials emerged from Japan indicating attractive regimens that include S-1 for advanced gastric cancer patients.Using these active anticancer drugs,the trials that studied the eff icacy of adjuvant therapies or surgical approaches,such as the Int-116/MAGIC/ACTS-GC trials,have actually succeeded in demonstrating the benefits of adjuvant therapies in gastric cancer patients.For cases of gastric cancer in elderly patients,treatment policies should consider these studies while analyzing not only the therapeutic effects but also drug toxicity,individual general health conditions,and social factors to select treatments that emphasize quality of life.展开更多
AIM: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups. METHODS: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified fro...AIM: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups. METHODS: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage Ⅱ or Ⅲ gastric cancer patients 】 18 years of age who underwent curative-intentsurgical resection. Patients were categorized into three groups according to the receipt of chemotherapy:(1) no chemotherapy;(2) preoperative chemotherapy; or(3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms.RESULTS: Of 1518 patients with surgically resected gastric cancer, 327(21.5%) received perioperative chemotherapy. The majority of these 327 patients were male(68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients(mean age, 70.7; P 【 0.001). Most patients had tumors frequently located in the distal stomach(34.5%). Preoperative chemotherapy was administered to 11.3% of patients(n = 37) and postoperative therapy to 88.7% of patients(n = 290). An overall survival benefit according to timing of chemotherapy was not observed on univariate or multivariate analysis. Similar results were observed with stagespecific survival analyses(5-year overall survival: Stage Ⅱ, 25% vs 30%, respectively; Stage Ⅲ, 14% vs 11%, respectively). Therefore, our results do not identify a survival advantage for specific timing of chemotherapy in locally advanced gastric cancer. CONCLUSION: This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer.展开更多
BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are f...BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.展开更多
To the Editor:Recently,the advantages of peri-operative chemotherapy in downstaging tumor and improving patient survival have been reported. Herein, we report a case of gastric cancer patient receiving neoadjuvant che...To the Editor:Recently,the advantages of peri-operative chemotherapy in downstaging tumor and improving patient survival have been reported. Herein, we report a case of gastric cancer patient receiving neoadjuvant chemotherapy along with trastuzumab and nivolumab.展开更多
文摘BACKGROUND It is unclear whether treatment delay affects the clinical outcomes of chemotherapy in advanced gastric cancer(A-GC).AIM To assess whether treatment delay affects the clinical outcomes of chemotherapy in A-GC.METHODS This single-center retrospective study examined consecutive patients with A-GC between April 2012 and July 2018. In total, 110 patients with stage Ⅳ A-GC who underwent chemotherapy were enrolled. We defined the wait time(WT) as the interval between diagnosis and chemotherapy initiation. We evaluated the influence of WT on overall survival(OS).RESULTS The mean OS was 303 d. The median WT was 17 d. We divided the patients into early and elective WT groups, with a 2-wk cutoff point. There were 46 and 64 patients in the early and elective WT groups, respectively. Compared with the elective WT group, the early WT group had significantly lower albumin(Alb)levels and higher neutrophil/lymphocyte ratios and C-reactive protein(CRP)levels but not a lower performance status. The elective WT group underwent more combination chemotherapy than did the early WT group. OS was different between the two groups(230 d vs 340 d, respectively). Multivariate analysis revealed that higher CRP levels, lower Alb levels and monotherapy were significantly related to a poor prognosis. To minimize potential selection bias,patients in the elective WT group were 1:1 propensity score matched with patients in the early WT group; no significant difference in OS was found(303 d vs 311 d, respectively, log-rank P = 0.9832).CONCLUSION A longer WT in patients with A-GC does not appear to be associated with a worse prognosis.
基金Supported by the Beijing Municipal Science and Technology Plan,No.D141100000414002the National Natural Science Foundation of China,No.81272698,No.81672319,and No.81602507
文摘AIM To evaluate whether the neoadjuvant chemotherapy(NAc T)-surgery interval time significantly impacts the pathological complete response(pc R) rate and longterm survival.METHODS One hundred and seventy-six patients with gastric cancer undergoing NAc T and a planned gastrectomy at the chinese p LA General hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NAc T-surgery interval time(< 4 wk, 4-6 wk, and > 6 wk) on pc R rate and overall survival(OS).RESULTS The NAc T-surgery interval time and clinician T stage were independent predictors of pc R. The interval time > 6 wk was associated with a 74% higher odds of pc R as compared with an interval time of 4-6 wk(p = 0.044), while the odds ratio(OR) of clinical T3 vs clinical T4 stage for pc R was 2.90(95%c I: 1.04-8.01, p = 0.041). In cox regression analysis of long-term survival, postneoadjuvant therapy pathological N(yp N) stage significantly impacted OS(N0 vs N3: h R = 0.16, 95%c I: 0.37-0.70, p = 0.015; N1 vs N3: h R = 0.14, 95%c I: 0.02-0.81, p = 0.029) and disease-free survival(DFS)(N0 vs N3: h R = 0.11, 95%c I: 0.24-0.52, p = 0.005; N1 vs N3: h R = 0.17, 95%c I: 0.02-0.71, p = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12(95%c I: 0.33-0.42, p = 0.001) for OS, and 0.13(95%c I: 0.36-0.44, p = 0.001) for DFS.CONCLUSION The NAc T-surgery interval time is associated with pc R but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pc R.
文摘With the increase in average life expectancy,the rate of occurrence of gastric cancer in elderly patients is also rising.While many clinical trials have been conducted to examine the effect of chemotherapy treatment on gastric cancer,age limits for eligible subjects have prevented the establishment of standards for chemotherapy in elderly patients with gastric cancer.As of March 2009,evidence-based standard chemotherapy regimens were established.In the Western world,debates centered on the ECF(Epirubicin/cisplatin/5FU) or DCF(Docetaxel/cisplatin/5-FU) regimens based on the phase □ randomized controlled trial at the Royal Marsden Hospital(RMH) or the V325 study,respectively.The JCOG9912 and SPIRITS trials emerged from Japan indicating attractive regimens that include S-1 for advanced gastric cancer patients.Using these active anticancer drugs,the trials that studied the eff icacy of adjuvant therapies or surgical approaches,such as the Int-116/MAGIC/ACTS-GC trials,have actually succeeded in demonstrating the benefits of adjuvant therapies in gastric cancer patients.For cases of gastric cancer in elderly patients,treatment policies should consider these studies while analyzing not only the therapeutic effects but also drug toxicity,individual general health conditions,and social factors to select treatments that emphasize quality of life.
文摘AIM: To evaluate the timing of chemotherapy in gastric cancer by comparing survival outcomes in treatment groups. METHODS: Patients with surgically resected gastric adenocarcinoma from 1988 to 2006 were identified from the Los Angeles County Cancer Surveillance Program. To evaluate the population most likely to receive and/or benefit from adjunct chemotherapy, inclusion criteria consisted of Stage Ⅱ or Ⅲ gastric cancer patients 】 18 years of age who underwent curative-intentsurgical resection. Patients were categorized into three groups according to the receipt of chemotherapy:(1) no chemotherapy;(2) preoperative chemotherapy; or(3) postoperative chemotherapy. Clinical and pathologic characteristics were compared across the different treatment arms.RESULTS: Of 1518 patients with surgically resected gastric cancer, 327(21.5%) received perioperative chemotherapy. The majority of these 327 patients were male(68%) with a mean age of 61.5 years; and they were significantly younger than non-chemotherapy patients(mean age, 70.7; P 【 0.001). Most patients had tumors frequently located in the distal stomach(34.5%). Preoperative chemotherapy was administered to 11.3% of patients(n = 37) and postoperative therapy to 88.7% of patients(n = 290). An overall survival benefit according to timing of chemotherapy was not observed on univariate or multivariate analysis. Similar results were observed with stagespecific survival analyses(5-year overall survival: Stage Ⅱ, 25% vs 30%, respectively; Stage Ⅲ, 14% vs 11%, respectively). Therefore, our results do not identify a survival advantage for specific timing of chemotherapy in locally advanced gastric cancer. CONCLUSION: This study supports the implementation of a randomized trial comparing the timing of perioperative therapy in patients with locally advanced gastric cancer.
基金Supported by TMH-IRG(account number-466/2012 and 164/2016)LTMT grant for project funding+1 种基金ACTREC-TMC for funding to Gupta labsupported by ACTREC fellowships
文摘BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.
文摘To the Editor:Recently,the advantages of peri-operative chemotherapy in downstaging tumor and improving patient survival have been reported. Herein, we report a case of gastric cancer patient receiving neoadjuvant chemotherapy along with trastuzumab and nivolumab.
