Efficacy and safety of bevacizumab plus chemotherapy in Chinese patients with metastatic colorectal cancer:a randomized phase Ⅲ ARTIST trial

The efficacy and safety of bevacizumab with modified irinotecan,leucovorin bolus,and 5-fluorouracil intravenous infusion(mIFL) in the first-line treatment of metastatic colorectal cancer(mCRC) has not been well evaluated in randomized clinical trials in Chinese patients.We conducted a phrase Ⅲ trial in which patients with previously untreated mCRC were randomized 2:1 to the mIFL [irinotecan(125 mg/m2),leucovorin(20 mg/m2) bolus,and 5-fluorouracil intravenous infusion(500 mg/m2) weekly for four weeks every six weeks] plus bevacizumab(5 mg/kg every two weeks) group and the mIFL group,respectively.Co-primary objectives were progression-free survival(PFS) and 6-month PFS rate.In total,214 patients were enrolled.Our results showed that addition of bevacizumab to mIFL significantly improved median PFS(4.2 months in the mIFL group vs.8.3 months in the bevacizumab plus mIFL group,P < 0.001),6-month PFS rate(25.0% vs.62.6%,P < 0.001),median overall survival(13.4 months vs.18.7 months,P = 0.014),and response rate(17% vs.35%,P = 0.013).Grades 3 and 4 adverse events included diarrhea(21% in the mIFL group and 26% in the bevacizumab plus mIFL group) and neutropenia(19% in the mIFL group and 33% in the bevacizumab plus mIFL group).No wound-healing complications or congestive heart failure occurred.Our results suggested that bevacizumab plus mIFL is effective and well tolerated as first-line treatment for Chinese patients with mCRC.Clinical benefit and safety profiles were consistent with those observed in pivotal phase Ⅲ trials with mainly Caucasian patients.

Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer

Background: Complete resection of locally advanced sigmoid colon cancer(LASCC) is sometimes difficult. Patients with LASCC have a dismal prognosis and poor quality of life, which has encouraged the evaluation of alternative multimodality treatments. This prospective study aimed to assess the feasibility and efficacy of neoadjuvant chemora?diotherapy(neo CRT) followed by surgery as treatment of selected patients with unresectable LASCC.Methods: We studied the patients with unresectable LASCC who received neo CRT followed by surgery between October 2010 and December 2012. The neoadjuvant regimen consisted of external?beam radiotherapy to 50 Gy and capecitabine?based chemotherapy every 3 weeks. Surgery was scheduled 6–8 weeks after radiotherapy.Results: Twenty?one patients were included in this study. The median follow?up was 42 months(range, 17–57 months). All patients completed neo CRT and surgery. Resection with microscopically negative margins(R0 resection) was achieved in 20 patients(95.2%). Pathologic complete response was observed in 8 patients(38.1%). Multivisceral resection was necessary in only 7 patients(33.3%). Two patients(9.5%) experienced grade 2 postopera?tive complications. No patients died within 30 days after surgery. For 18 patients with pathologic M0(yp M0) disease, the cumulative probability of 3?year local recurrence?free survival, disease?free survival and overall survival was 100.0%, 88.9% and 100.0%, respectively. For all 21 patients, the cumulative probability of 3?year overall survival was 95.2% and bladder function was well preserved.Conclusion: For patients with unresectable LASCC, preoperative chemoradiotherapy and surgery can be performed safely and may result in an increased survival rate.

HBV infection decreases risk of liver metastasis in patients with colorectal cancer:A cohort study

AIM:To evaluate the effect of hepatitis B virus (HBV) infection on liver metastasis of colorectal cancer.METHODS:A total of 1298 colorectal cancer patients were recruited from January 2001 to March 2005 in this study.Enzyme-linked immunosorbent assay was used to test serum HBV markers for colorectal cancer.Patients were divided into study (infection) group and control (non-infection) group.Clinical features of patients in two groups were compared.RESULTS:Liver metastasis was found in 319 out of the 1298 colorectal cancer patients.The incidence of liver metastasis was significantly lower in study group than in control group (14.2% vs 28.2%,P < 0.01).HBV infection significantly decreased the risk of liver metastasis [hazard ratio (HR):0.50,95% confidence interval (95% CI):0.38-0.66],but the incidence of extrahepatic metastasis was significantly higher in study group than in control group (31.9% vs 17.0%,P < 0.01).The HR was the lowest in chronic hepatitis B group (HR:0.29,95% CI:0.12-0.72).The number of liver metastatic lesions was significantly less in study group than in control group with a higher surgical resection rate.However,no significant difference was found in survival rate between the two groups (P=0.95).CONCLUSION:HBV infection decreases the risk of liver metastasis in patients with colorectal cancer and elevates the surgical resection rate of liver metastatic lesions.

Expert consensus on maintenance treatment for metastatic colorectal cancer in China

The impact of maintenance therapy on progression-free survival and overall survival as well as quality of life of Chinese patients with metastatic colorectal cancer has long been under discussion.Recently,some phase III clinical trials have revealed that maintenance therapy can significantly prolong the progression-free survival while maintain an acceptable safety profile.Based on this evidence and common treatment practice in China,we now generated one Expert Consensus on Maintenance Treatment for Metastatic Colorectal Cancer in China to further specify the necessity of maintenance therapy,suitable candidates for such treatment,and appropriate regimens.

Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer

AIM: To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.

Predictive and prognostic biomarkers with therapeutic targets in advanced colorectal cancer

Colorectal cancer(CRC)is one of the most common human malignant diseases and the second leading cause of cancer-related deaths worldwide.The treatment of advanced CRC has improved significantly in recent years.With the emergence of two targeted antibodies,cetuximab(Erbitux),an anti-epidermal growth factor receptor monoclonal antibody and bevacizumab(Avastin),a vascular endothelial growth factor monoclonal antibody,the treatment of metastatic CRC has entered the era of personalized therapy.Predictive and prognostic biomarkers have,and will continue to,facilitate the selection of suitable patients and the personalization of treatment for metastatic CRC(mCRC).In this review,we will focus primarily on the important progresses made in the personalized treatment of mCRC and discuss the potentially novel predictive and prognostic biomarkers for improved selection of patients for anti-cancer treatment in the future.

Healing time of incision infection after hepatobiliary surgery treated by needle-free incision suture closure

AIM: To compare the effectiveness of needle-free incision suture closure with butterfly tape and traditional secondary suturing techniques in treating incision infection. METHODS: Two hundred and twenty-three patients with incision infection following hepatobiliary surgery at a tertiary hospital were randomly divided into three groups: 90 patients were closed by needle-free incision suture closure, which gradually closed the incision wound when drainage from incision infection was visibly decreased and healthy granulation tissues had grown; 79 patients were closed by butterfly bandage; another 54 patients were closed by traditional secondary suturing technique. Healing time of incision infection was calculated from the beginning of dressing change to the healing of the incision. RESULTS: Healing time in the needle-free incision suture closure group (24.2 +/- 7.2 d) was significantly shorter than that in the butterfly bandage group (33.3 +/- 11.2 d) and the traditional secondary suturing group (36.2 +/- 15.3 d) (P < 0.05). Healing time in the butterfly bandage group appeared to be slightly shorter than that in the secondary suture group, but the difference was not statistically significant (P > 0.05). CONCLUSION: Needle-free incision suture closure could gradually close the infection wound at the same time of drainage and dressing change, thereby shortening the healing time. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases

Background: Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorecal cancer patients with liver metastases who underwent hepatectomy.However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients.Patients and methods: In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients.The pathologic response was evaluated according to the tumor regression grade(TRG).The prognostic role of pathologic response in recurrence-free survival(RFS) and overall survival(OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests.Results: Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy(median RFS: 9.9 vs.6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors,and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases(all P < 0.05). A decrease in the serum carcinoembryonic antigen(CEA) level after preoperative chemotherapy predicted an increased pathologic response rate(P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens.Conclusions: We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

PhaseⅡstudy of oxaliplatin combined with S-1 and leucovorin(SOL)for Chinese patients with metastatic colorectal cancer

Background:Fluoropyrimidine and oxaliplatin are widely used for patients with colorectal cancer.This phase II study was conducted to evaluate the efficacy and safety of the combination of S-1,oxaliplatin,and leucovorin(SOL) in the treatment of Chinese patients with metastatic colorectal cancer(mCRC).Methods:Eligible patients with untreated mCRC from four hospitals in China received intravenous oxaliplatin(85 mg/m2) on day 1,oral S-1 twice daily(80-120 mg per day) on day 1-7,and leucovorin twice daily(50 mg per day)simultaneously with S-1,every 2 weeks.Results and discussion:Forty patients were enrolled in our study.In total,296 cycles of SOL were administered.The overall response rate was 50.0%.At a median follow-up of 27 months,progression-free survival and overall surviva were 7.0 months(95%confidence interval[CI]6.0-10.6 months) and 22.2 months(95%CI 15.1-29.3 months),respectively.The most common grade 3/4 non-hematological adverse events were diarrhea(n = 8,20.0%),nausea(n = 3,7.5%),and vomiting(n = 3,7.5%).The most common grade 3/4 hematological toxicities were thrombocytopenia(n = 3,7.5%),neutropenia(n = 1,2.5%),and abnormal alanine transaminase/aspartate transaminase levels(n = 1,2.5%).There was one treatment-related death.Conclusions:The data indicate that the SOL regimen is effective and moderately tolerated in Chinese patients with mCRC.Trial registration:Clinical trial

Characterization of E-cadherin expression in normal mucosa,dysplasia and adenocarcinoma of gastric cardia and its influence on prognosis

BACKGROUND Gastric cardia adenocarcinoma(GCA),which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries,is of similar geographic distribution with esophageal squamous cell carcinoma in China,and even referred as"sister cancer"by Chinese oncologists.The molecular mechanism for GCA is largely unknown.Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers.However,the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis.AIM To characterize E-cadherin expression in normal gastric cardia mucosa,dysplasia and GCA tissues,and its influence on prognosis for GCA.METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases.The enrollment criteria included radical surgery for GCA,but without any radio-or chemo-therapy before operation.The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue(n=208)and dysplasia lesions(n=156)were collected,and processed as tissue microarray for immunohistochemistry.The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter,telephone or home interview.E-cadherin protein expression was determined by two step immunohistochemistry.Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients.RESULTS Of the 4561 GCA patients,there were 3607 males with a mean age of 61.6±8.8 and 954 females with a mean age of 61.9±8.6 years,respectively.With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA,the positive immunostaining rates for E-cadherin decreased significantly from 100%to 93.0%and 84.1%,respectively(R2=0.9948).Furthermore,E-cadherin positive immunostaining rate was significantly higher in patients at early stage(0 and I)than in those at late stage(II and III)(92.7%vs 83.7%,P=0.001).E-cadherin positive expression rate was significantly associated with degree of differentiation(P=0.001)and invasion depth(P<0.001).Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative(P=0.026).It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis.However,in patients with negative lymph node metastasis,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.036).Similarly,in patients with late stage GCA,those with positive expression of E-cadherin had better survival than those with negative expression(P=0.011).CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer:a multicenter,randomized,double-blinded,placebo-controlled,phaseⅡclinical trial

Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in mCRC.Methods: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and safety.Results: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable tolerability.Trial registration This study was registered on ClinicalTrials.gov(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal

The Chinese Journal of Cancer is indexed in Science CitationIndex(SCI) Expanded

On July 22,2014,the Chinese Journal of Cancer(CJC)received a notification from Thomson Reuters that the publications of our journal starting from 2012 have been accepted for coverage in Science Citation Index Expanded,available at the Web of Science,Core Collection,Biological Abstracts,and Biosis Previews.What this means in practical terms is that CJC will receive its first official impact factor(IF)in 2015.This is an important milestone in the history

Adjuvant chemotherapy,p53,carcinoembryonic antigen expression and prognosis after D2 gastrectomy for gastric adenocarcinoma

AIM: To investigate adjuvant chemotherapy, p53 and carcinoembryonic antigen (CEA) expression and prognosis after D2 gastrectomy for stage II/III gastric adenocarcinoma.

Preoperative maximal voluntary ventilation,hemoglobin,albumin,lymphocytes and platelets predict postoperative survival in esophageal squamous cell carcinoma

BACKGROUND Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications.Reduced pulmonary function is associated with poor survival in several cancers,but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma(ESCC)is unclear.Nutritional and systemic inflammation parameters are vital to cancer survival,and the combination of these parameters improves the prognostic value.The hemoglobin,albumin,lymphocytes and platelets(HALP)score is a novel prognostic indicator to reflect the nutritional and inflammation status,but the clinical effects of the HALP score combined with maximal voluntary ventilation(MVV),an important parameter of pulmonary function,have not been well studied in ESCC.AIM To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients.METHODS Data form 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed.Preoperative MVV and HALP data were retrieved from medical archives.The HALP score was calculated by the formula:Hemoglobin(g/L)×albumin(g/L)×lymphocytes(/L)/platelets(/L).The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis.The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested.Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival.RESULTS MVV was significantly associated with gender(P<0.001),age at diagnosis(P<0.001),smoking history(P<0.001),drinking history(P<0.001),tumor length(P=0.013),tumor location(P=0.037)and treatment type(P=0.001).The HALP score was notably associated with gender(P<0.001),age at diagnosis(P=0.035),tumor length(P<0.001)and invasion depth(P=0.001).Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival(all P<0.001).Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival(all P<0.001).The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis.Also,low combination of MVV and HALP score was an independent risk factor for poor overall survival(P<0.001).CONCLUSION MVV,HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.

Defeating cancer:the 150 most important questions in cancer research and clinical oncology

Despite all the human efforts and monetary investment over the last few decades,cancer is still a devastating threat to our life expectancy and quality of life in many parts of the world.The etiology of cancer varies.The genetic and epigenetic causes of cancer are heterogeneous and multifaceted.Early detection is still a

Development and validation of a prognostic nomogram model for Chinese patients with primary small cell carcinoma of the esophagus

BACKGROUND Primary small cell carcinoma of the esophagus(PSCE)is a highly invasive malignant tumor with a poor prognosis compared with esophageal squamous cell carcinoma.Due to the limited samples size and the short follow-up time,there are few reports on elucidating the prognosis of PSCE,especially on the establishment and validation of a survival prediction nomogram model covering general information,pathological factors and specific biological proteins of PSCE patients.AIM To establish an effective nomogram to predict the overall survival(OS)probability for PSCE patients in China.METHODS The nomogram was based on a retrospective study of 256 PSCE patients.Univariate analysis and multivariate Cox proportional hazards regression analysis were used to examine the prognostic factors associated with PSCE,and establish the model for predicting 1-,3-,and 5-year OS based on the Akaike information criterion.Discrimination and validation were assessed by the concordance index(C-index)and calibration curve and decision curve analysis(DCA).Histology type,age,tumor invasion depth,lymph node invasion,detectable metastasis,chromogranin A,and neuronal cell adhesion molecule 56 were integrated into the model.RESULTS The C-index was prognostically superior to the 7th tumor node metastasis(TNM)staging in the primary cohort[0.659(95%CI:0.607-0.712)vs 0.591(95%CI:0.517-0.666),P=0.033]and in the validation cohort[0.700(95%CI:0.622-0.778)vs 0.605(95%CI:0.490-0.721),P=0.041].Good calibration curves were observed for the prediction probabilities of 1-,3-,and 5-year OS in both cohorts.DCA analysis showed that our nomogram model had a higher overall net benefit compared to the 7th TNM staging.CONCLUSION Our nomogram can be used to predict the survival probability of PSCE patients,which can help clinicians to make individualized survival predictions.

Increased prognostic value of clinical–reproductive model in Chinese female patients with esophageal squamous cell carcinoma

BACKGROUND In China,it has been well recognized that some female patients with esophageal squamous cell carcinoma(ESCC)have different overall survival(OS)time,even with the same tumor-node-metastasis(TNM)stage,challenging the prognostic value of the TNM system alone.An effective predictive model is needed to accurately evaluate the prognosis of female ESCC patients.AIM To construct a novel prognostic model with clinical and reproductive data for Chinese female patients with ESCC,and to assess the incremental prognostic value of the full model compared with the clinical model and TNM stage.METHODS A new prognostic nomogram incorporating clinical and reproductive features was constructed based on univariatie and Cox proportional hazards survival analysis from a training cohort(n=175).The results were recognized using the internal(n=111)and independent external(n=85)validation cohorts.The capability of the clinical–reproductive model was evaluated by Harrell’s concordance index(C-index),Kaplan–Meier curve,time-dependent receiver operating characteristic(ROC),calibration curve and decision curve analysis.The correlations between estrogen response and immune-related pathways and some gene markers of immune cells were analyzed using the TIMER 2.0 database.RESULTS A clinical–reproductive model including incidence area,age,tumor differentiation,lymph node metastasis(N)stage,estrogen receptor alpha(ESR1)and beta(ESR2)expression,menopausal age,and pregnancy number was constructed to predict OS in female ESCC patients.Compared to the clinical model and TNM stage,the time-dependent ROC and C-index of the clinical–reproductive model showed a good discriminative ability for predicting 1-,3-,and 5-years OS in the primary training,internal and external validation sets.Based on the optimal cut-off value of total prognostic scores,patients were classified into high-and low-risk groups with significantly different OS.The estrogen response was significantly associated with p53 and apoptosis pathways in esophageal cancer.CONCLUSION The clinical–reproductive prognostic nomogram has an incremental prognostic value compared with the clinical model and TNM stage in predicting OS in Chinese female ESCC patients.

Temporal Change in Treatment Patterns of Metastatic Colorectal Cancer and Its Association with Patient Survival:A Retrospective Cohort Study Based on an Intelligent Big-Data Platform

There is a lack of high-quality,large-scale,real-world evidence from patients with metastatic colorectal cancer(mCRC),especially in China.It remains unclear whether efforts to improve the quality of care for mCRC would improve patient survival outcomes in real-world practice.On the basis of an intelligent bigdata platform,we established a large-scale retrospective cohort of mCRC patients.We investigated the temporal changes in the systemic and local treatment(resection,ablation,or radiation to liver,lung,or extrahepatic and/or extrapulmonary metastases)patterns of mCRC,and whether these changes were associated with improved overall survival(OS)over time.Between July 2012 and December 2018,3403 eligible patients were included in this research.The median OS was 42.8 months(95%confidence interval(CI),40.7–46.6)for the entire cohort,25.6 months(95%CI,24.7–26.9)for those treated with systemic therapy only,and not reached(95%CI,78.6 months–not reached)for those receiving local therapy.The utility rate of local therapy increased continuously from 37.9%in 2012–2014 to 46.9%in 2017–2018.A dramatic increase in the utility rate of either cetuximab or bevacizumab was observed since 2017(39.9%,43.2%,and 60.3%in 2012–2014,2015–2016,and 2017–2018,respectively).Compared with 2012–2014,the OS of the entire population significantly improved in 2015–2016(hazard ratio(HR)=0.87(95%CI,0.78–0.99);P=0.034),but not for patients receiving systemic therapy only(HR=0.99(95%CI,0.86–1.14);P=0.889),whereas an improved OS was found in 2015–2018 for both the entire population(HR=0.75(95%CI,0.70–0.81);P<0.001)and for patients receiving systemic therapy only(HR=0.83(95%CI,0.77–0.91);P<0.001).In summary,the quality of care for mCRC,as indicated by the utility rate of targeted and local therapies,has been continuously improving over time in this study cohort,which is associated with continuously improving survival outcomes for these patients.

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023

The 2023 update of the Chinese Society of Clinical Oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision medicine.These updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer patients.Key revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric cancer.For advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2(HER2)-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)patients.Additionally,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer.The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of China,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

A phase II clinical trial of toripalimab in advanced solid tumors with polymerase epsilon/polymerase delta(POLE/POLD1)mutation

Patients carrying mutations in polymerase epsilon/polymerase delta have shown positive responses to immune checkpoint inhibitors.Yet,prospective trials exploring the efficacy in those with polymerase epsilon/polymerase delta mutations are still lacking.A phase II clinical trial was initiated to evaluate the efficacy of toripalimab,a humanized IgG4K monoclonal antibody to human PD-1,in patients with advanced solid tumors with unselected polymerase epsilon/polymerase delta mutations but without microsatellite instability-high.A total of 15 patients were enrolled,14 of whom were assessed for treatment efficacy.There was a 21.4%overall response rate,with a disease control rate of 57.1%.The median overall survival and median progression-free survival were 17.9(95%CI 13.5-not reach)months and 2.5(95%CI 1.4-not reach)months,respectively.For patients with exonuclease domain mutations,the objective response rate was 66.7%(2/3),with a disease control rate of 66.7%(2/3).For those with non-exonuclease domain mutations,the rates were 9.1%(1/11)and 54.5%(6/11),respectively.Notably,patients with PBRM1 gene mutations exhibited a high response rate to toripalimab at 75.0%(3/4).This study showed that neither the exonuclease domain mutations nor non-exonuclease domain mutations could fully predict the efficacy of immunotherapy,urging the need for more investigations to clarify potential immune sensitization differences within polymerase epsilon/polymerase delta mutation variants.