Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced re...Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.展开更多
BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in ...BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in real-world patients with GCOM,the survival rates and efficacy of metastatic vs non-metastasized resection.AIM To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM.METHODS This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People’s Hospital from June 2009 to July 2023.The diagnosis of all patients was confirmed by pathology.The primary study endpoints included overall survival(OS),ovarian survival,OS after surgery(OSAS),disease-free survival(DFS),differences in efficacy.RESULTS This study had 41 patients in total.The surgical group(n=27)exhibited significantly longer median OS(mOS)and median overall months(mOM)compared to the nonoperative group(n=14)(mOS:23.0 vs 6.9 months,P=0.015;mOM:18.3 vs 3.8 months,P=0.001).However,there were no significant differences observed in mOS,mOM,median OSAS(mOSAS),and median DFS(mDFS)between patients in the surgical resection plus neoadjuvant therapy group(n=11)and those who surgical resection without neoadjuvant therapy group(n=16)(mOS:26.1 months vs 21.8 months,P=0.189;mOM:19.8 vs 15.2 months,P=0.424;mOSAS:13.9 vs 8.7 months,P=0.661,mDFS:5.1 vs 8.2 months,P=0.589).CONCLUSION Compared to the non-surgical group,the surgical group’s survival duration and efficacy are noticeably longer.The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.展开更多
BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is sparse.AIM To synthesise evidence on NAT fo...BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is sparse.AIM To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial involvement.METHODS A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT.All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database.Baseline characteristics,NAT type,progression to surgery and oncological outcomes were collected.RESULTS Twelve studies were included.The definition of“unresectable”locally advanced dCCA was heterogenous.Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most cases.Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA.The presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced disease.Three patients progressed to surgery and 2 were resected.One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months postoperatively.CONCLUSION Evidence for benefit of NAT is limited.Consensus on criteria for uniform definition of resectability for dCCA is required.We propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.展开更多
BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically col...BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.展开更多
BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predi...BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.展开更多
Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] th...Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.展开更多
Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the...Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.展开更多
Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly...Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.展开更多
BACKGROUND Laparoscopic gastrectomy(LG)is widely accepted as a minimally invasive approach for the treatment of early gastric cancer.However,its role in locally advanced gastric cancer(LAGC)after neoadjuvant therapy(N...BACKGROUND Laparoscopic gastrectomy(LG)is widely accepted as a minimally invasive approach for the treatment of early gastric cancer.However,its role in locally advanced gastric cancer(LAGC)after neoadjuvant therapy(NAT)remains controversial.This study aimed to compare the efficacy and safety of LG vs open gastrectomy(OG)after NAT for the treatment of LAGC.AIM To compare the efficacy and safety of LG vs OG after NAT for LAGC.METHODS We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG(n=38)or OG(n=38)between 2021 and 2023.The primary endpoint was overall survival(OS),and the secondary endpoints were diseasefree survival(DFS),surgical complications,and quality of life(QOL).RESULTS The two groups had comparable baseline characteristics,with a median follow-up period of 24 mo.The 3-year OS rates in the LG and OG groups were 68.4%and 60.5%,respectively(P=0.42).The 3-year DFS rates in the LG and OG groups were 57.9%and 50.0%,respectively(P=0.51).The LG group had significantly less blood loss(P<0.001),a shorter hospital stay(P<0.001),and a lower incidence of surgical site infection(P=0.04)than the OG group.There were no significant differences in other surgical complications between the groups,including anastomotic leakage,intra-abdominal abscess,or wound dehiscence.The LG group had significantly better QOL scores than the OG group regarding physical functioning,role functioning,global health status,fatigue,pain,appetite loss,and body image at 6 months postoperatively(P<0.05).CONCLUSION LG after NAT is a viable and safe alternative to OG for the treatment of LAGC,with similar survival outcomes and superior short-term recovery and QOL.LG patients had less blood loss,shorter hospitalizations,and a lower incidence of surgical site infections than OG patients.Moreover,the LG group had better QOL scores in multiple domains 6 mo postoperatively.Therefore,LG should be considered a valid option for patients with LAGC who undergo NAT,particularly for those who prioritize postoperative recovery and QOL.展开更多
BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for...BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for clinical stage II/III rectal cancer.However,few patients achieve a complete pathological response,and most patients require surgical resection and adjuvant therapy.Therefore,identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival(OS)and disease-free survival(DFS)for LARC treated with NT.METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017.The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors,which were validated by the Cox regression method.Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves,and that of the two nomograms was conducted by calculating the concordance index(C-index)and calibration curves.The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model:Vascular_tumors_bolt,cancer nodules,yN,body mass index,matchmouth distance from the edge,nerve aggression and postoperative carcinoembryonic antigen.The nomogram showed good predictive value for OS,with a C-index of 0.91(95%CI:0.85,0.97)and good calibration.In the validation cohort,the C-index was 0.69(95%CI:0.53,0.84).The risk factor prediction model showed good predictive value.The areas under the curve for 3-and 5-year survival were 0.811 and 0.782.The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77(95%CI:0.69,0.85).In the validation cohort,the C-index was 0.71(95%CI:0.61,0.81).The prediction model for DFS also had good predictive value,with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.展开更多
Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection prov...Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.展开更多
Gastric cancer is one of the most common digestive system tumors in China,and locally advanced gastric cancer(LAGC)accounts for a high proportion of newly diagnosed cases.Although surgery is the main treatment for gas...Gastric cancer is one of the most common digestive system tumors in China,and locally advanced gastric cancer(LAGC)accounts for a high proportion of newly diagnosed cases.Although surgery is the main treatment for gastric cancer,surgical excision alone cannot achieve satisfactory outcomes in LAGC patients.Neoadjuvant therapy(NAT)has gradually become the standard treatment for patients with LAGC,and this treatment can not only achieve tumor downstaging and improve surgical rate and the R0 resection rate,but it also significantly improves the long-term prognosis of patients.Peri/preoperative neoadjuvant chemotherapy and preoperative chemoradiotherapy are both recommended according to a large number of studies,and the regimens have also been evolved in the past decades.Since the NCCN guidelines for gastric cancer are one of the most authoritative evidence-based guidelines worldwide,here,we demonstrate the development course and major breakthroughs of NAT for gastric cancer based on the vicissitudes of the NCCN guidelines from 2007 to 2019,and also discuss the future of NAT.展开更多
BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC) with lymph node metastasis is poor.The feasibility of surgery is not certain,which is a contraindication according to the National Comprehensive Cancer ...BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC) with lymph node metastasis is poor.The feasibility of surgery is not certain,which is a contraindication according to the National Comprehensive Cancer Network guidelines.The role of immunotherapy as a neoadjuvant therapy for ICC is not clear.We herein describe a case of ICC with lymph node metastasis that was successfully treated with neoadjuvant therapy.CASE SUMMARY A 60-year-old man with a liver tumor was admitted to our hospital.Enhanced computed tomography and magnetic resonance imaging revealed a spaceoccupying lesion in the right lobe of the liver.Multiple subfoci were found around the tumor,and the right posterior branch of the portal vein was invaded.Liver biopsy indicated poorly differentiated cholangiocytes.According to the American Joint Committee on Cancer disease stage classification,ICC with hilar lymph node metastasis(stage ⅢB) and para-aortic lymph node metastasis was suspected.A report showed that two patients with stage ⅢB ICC achieved a complete response(CR) 13 mo and 16 mo after chemotherapy with a PD-1 monoclonal antibody.After multidisciplinary consultation,the patient was given neoadjuvant therapy,surgical resection and lymph node dissection,and postoperative adjuvant therapy.After three rounds of PD-1 immunotherapy(camrelizumab) and two rounds of gemcitabine combined with cisplatin regimen chemotherapy,the tumor size was reduced.Therefore,a partial response was achieved.Exploratory laparotomy found that the lymph nodes of Group 16 were negative,and the tumor could be surgically removed.Therefore,the patient underwent right hemihepatectomy plus lymph node dissection.The patient received six rounds of chemotherapy and five rounds of PD-1 treatment postoperatively.After 8 mo of follow-up,no recurrence was found,and a CR was achieved.CONCLUSION Neoadjuvant therapy combined with surgical resection is useful for advanced-stage ICC.This is the first report of successful treatment of stage ⅢB ICC using neoadjuvant therapy with a PD-1 inhibitor.展开更多
BACKGROUND For locally advanced rectal cancer(LARC),standard therapy[consisting of neoadjuvant chemoradiotherapy(CRT),surgery,and adjuvant chemotherapy(ChT)]achieves excellent local control.Unfortunately,survival is s...BACKGROUND For locally advanced rectal cancer(LARC),standard therapy[consisting of neoadjuvant chemoradiotherapy(CRT),surgery,and adjuvant chemotherapy(ChT)]achieves excellent local control.Unfortunately,survival is still poor due to distant metastases,which remains the leading cause of death among these patients.In recent years,the concept of total neoadjuvant treatment(TNT)has been developed,whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIM To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODS In a retrospective study,we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT.High-risk for failure was defined according to the presence of at least one of the following factors:T4 stage;N2 stage;positive mesorectal fascia;extramural vascular invasion;positive lateral lymph node.TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin,CRT with capecitabine,and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin prior to surgery.The primary endpoint was pathological complete response(pCR).In total,72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTS Compared to standard therapy,TNT showed a higher proportion of pCR(23%vs 7%;P=0.01),a lower neoadjuvant rectal score(median:8.43 vs 14.98;P<0.05),higher T-and N-downstaging(70%and 94%vs 51%and 86%),equivalent R0 resection(95%vs 93%),shorter time to stoma closure(mean:20 vs 33 wk;P<0.05),higher compliance during systemic ChT(completed all cycles 87%vs 76%;P<0.05),lower proportion of acute toxicity grade≥3 during ChT(3%vs 14%,P<0.05),and equivalent acute toxicity and compliance during CRT and in the postoperative period.The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetricmodulated arc radiotherapy than with 3D conformal radiotherapy(32%vs 9%;P<0.05).CONCLUSION Compared to standard therapy,TNT provides better outcome for LARC patients with high-risk factors for failure,in terms of pCR and neoadjuvant rectal score.展开更多
Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuv...Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.展开更多
BACKGROUND Neoadjuvant therapy(NAT)is becoming increasingly important in locally advanced rectal cancer.Hence,such research has become a problem.AIM To evaluate the downstaging effect of NAT,its impact on postoperativ...BACKGROUND Neoadjuvant therapy(NAT)is becoming increasingly important in locally advanced rectal cancer.Hence,such research has become a problem.AIM To evaluate the downstaging effect of NAT,its impact on postoperative complications and its prognosis with different medical regimens.METHODS Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy(NRCT)group and the neoadjuvant chemotherapy(NCT)group.The differences between the two groups in tumor regression,postoperative complications,rectal function,disease-free survival,and overall survival were compared using theχ2 test and Kaplan-Meier analysis.RESULTS Baseline data showed no statistical differences between the two groups,whereas the NRCT group had a higher rate of T4(30/55 vs 5/22,P<0.05)than the NCT groups.Twelve cases were evaluated as complete responders,and 15 cases were evaluated as tumor regression grade 0.Except for the reduction rate of T stage(NRCT 37/55 vs NCT 9/22,P<0.05),there was no difference in effectiveness between the two groups.Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage.No significant difference in postoperative complications and disease-free survival between the two groups was observed,although the NRCT group might have better long-term overall survival.CONCLUSION NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor.Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.展开更多
BACKGROUND Laparoscopic total gastrectomy(LTG)has drawn increasing attention over the years.Although LTG has shown surgical benefits compared to open TG(OTG)in early stage gastric cancer(GC),little is known about the ...BACKGROUND Laparoscopic total gastrectomy(LTG)has drawn increasing attention over the years.Although LTG has shown surgical benefits compared to open TG(OTG)in early stage gastric cancer(GC),little is known about the surgical and oncological outcomes of LTG for advanced GC following neoadjuvant therapy(NAT).AIM To compare the long-and short-term outcomes of advanced GC patients who underwent LTG vs OTG following NAT.METHODS Advanced GC patients who underwent TG following NAT between April 2011 and May 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences were enrolled and stratified into two groups:LTG and OTG.Propensity score matching analysis was performed at a 1:1 ratio to overcome possible bias.RESULTS In total,185 patients were enrolled(LTG:78;OTG:109).Of these,138 were paired after propensity score matching.After adjustment for propensity score matching,baseline parameters were similar between the two groups.Compared to OTG,LTG was associated with a significantly shorter length of hospital stay(P=0.012).The rates of R0 resection,lymph node harvest,and postoperative morbidity did not significantly differ between the two groups.Overall survival(OS)outcomes were comparable between the two groups.Pathological T and N stages were found to be independent risk factors for OS.CONCLUSION LTG can be a feasible method for advanced GC patients following NAT,as it appears to be associated with better short-and comparable long-term outcomes compared to OTG.展开更多
In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only pote...In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only potential monomodal cure for pancreatic adenocarcinoma. However only 10%–20% of patients present with tumors that are amenable to resection, and even after resection of localized cancers, long term survival is rare. The addition of chemoradiation therapy significantly increases median survival. To achieve long-term success in treating this disease it is therefore increasingly important to identify effective neoadjuvant/adjuvant multimodality therapies. Preoperative chemoradiation for potentially resectable pancreatic cancer has the following advantages: (1) neoadjuvant treatment would eliminate the delay of adjuvant treatment due to postoperative complications; (2) neoadjuvant treatment could avoid unnecessary surgery for patients with metastatic disease evident on restaging after neoadjuvant therapy; (3) downstaging after neoadjuvant therapy may increase the likelihood for negative surgical margins; and (4) neoadjuvant treatment could prevent peritoneal tumor cell implantation and dissemination caused during surgery. This review systematically summarizes the current status, controversies, and prospects of neoadjuvant treatment of pancreatic cancer.展开更多
BACKGROUND The number of dissected lymph nodes(LNs)in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIM To investigate the prognostic impact of the number of LN dissected in recta...BACKGROUND The number of dissected lymph nodes(LNs)in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIM To investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODS We performed a systematic review and searched Pub Med,Embase(Ovid),MEDLINE(Ovid),Web of Science,and Cochrane Library from January 1,2000 until January 1,2020.Two reviewers examined all the publications independently and extracted the relevant data.Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment(LNs≥12 vs LNs<12).The primary endpoints were the overall survival(OS)and disease-free survival(DFS).RESULTS Nine articles were included in the meta-analyses.Statistical analysis revealed a statistically significant difference in OS[hazard ratio(HR)=0.76,95%confidence interval(CI):0.66-0.88,I2=12.2%,P=0.336],DFS(HR=0.76,95%CI:0.63-0.92,I2=68.4%,P=0.013),and distant recurrence(DR)(HR=0.63,95%CI:0.48-0.93,I2=30.5%,P=0.237)between the LNs≥12 and LNs<12 groups,but local recurrence(HR=0.67,95%CI:0.38-1.16,I2=0%,P=0.348)showed no statistical difference.Moreover,subgroup analysis of LN negative patients revealed a statistically significant difference in DFS(HR=0.67,95%CI:0.52-0.88,I2=0%,P=0.565)between the LNs≥12 and LNs<12 groups.CONCLUSION Although neoadjuvant therapy reduces LN production in rectal cancer,our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’OS,DFS,and DR.展开更多
While pancreatic cancer is still characterized by early systemic spread and poor outcomes,the treatment of this disease has changed significantly in recent years due to major advancements in systemic therapy and advan...While pancreatic cancer is still characterized by early systemic spread and poor outcomes,the treatment of this disease has changed significantly in recent years due to major advancements in systemic therapy and advanced surgical techniques.Broader use of effective neoadjuvant approaches combined with aggressive surgical operations within a multidisciplinary setting has improved outcomes.Borderline resectable pancreatic cancer is characterized by tumor vascular invasion,and is a setting where the combination of potent neoadjuvant chemotherapy and aggressive surgical methods,including vascular resections and reconstructions,shows its full potential.Hopefully,this will lead to improved local control and curative treatment in a number of patients with this aggressive malignancy.展开更多
基金supported by “San Ming” Project of Shenzhen, China (No. SZSM201612051)National Natural Science Foundation of China (No. 81972240)。
文摘Colorectal cancer has a high incidence and mortality rate in China, with the majority of cases being middle and low rectal cancer. Surgical intervention is currently the main treatment modality for locally advanced rectal cancer, with the common goal of improving oncological outcomes while preserving function. The controversy regarding the circumferential resection margin distance in rectal cancer surgery has been resolved. With the promotion of neoadjuvant therapy concepts and advancements in technology, treatment strategies have become more diverse.Following tumor downstaging, there is an increasing trend towards extending the safe distance of distal rectal margin. This provides more opportunities for patients with low rectal cancer to preserve their anal function.However, there is currently no consensus on the specific distance of distal resection margin.
文摘BACKGROUND Regarding when to treat gastric cancer and ovarian metastasis(GCOM)and whether to have metastatic resection surgery,there is presently debate on a global scale.The purpose of this research is to examine,in real-world patients with GCOM,the survival rates and efficacy of metastatic vs non-metastasized resection.AIM To investigate the survival time and efficacy of metastatic surgery and neoadjuvant therapy in patients with GCOM.METHODS This study retrospectively analyzed the data of 41 GCOM patients admitted to Zhejiang Provincial People’s Hospital from June 2009 to July 2023.The diagnosis of all patients was confirmed by pathology.The primary study endpoints included overall survival(OS),ovarian survival,OS after surgery(OSAS),disease-free survival(DFS),differences in efficacy.RESULTS This study had 41 patients in total.The surgical group(n=27)exhibited significantly longer median OS(mOS)and median overall months(mOM)compared to the nonoperative group(n=14)(mOS:23.0 vs 6.9 months,P=0.015;mOM:18.3 vs 3.8 months,P=0.001).However,there were no significant differences observed in mOS,mOM,median OSAS(mOSAS),and median DFS(mDFS)between patients in the surgical resection plus neoadjuvant therapy group(n=11)and those who surgical resection without neoadjuvant therapy group(n=16)(mOS:26.1 months vs 21.8 months,P=0.189;mOM:19.8 vs 15.2 months,P=0.424;mOSAS:13.9 vs 8.7 months,P=0.661,mDFS:5.1 vs 8.2 months,P=0.589).CONCLUSION Compared to the non-surgical group,the surgical group’s survival duration and efficacy are noticeably longer.The efficacy and survival time of the direct surgery group and the neoadjuvant therapy group did not differ significantly.
文摘BACKGROUND The use of neoadjuvant therapy(NAT)in distal cholangiocarcinoma(dCCA)with regional arterial or extensive venous involvement,is not widely accepted and evidence is sparse.AIM To synthesise evidence on NAT for dCCA and present the experience of a highvolume tertiary-centre managing dCCA with arterial involvement.METHODS A systematic review was performed according to PRISMA guidance to identify all studies reporting outcomes of patients with dCCA who received NAT.All patients from 2017 to 2022 who were referred for NAT for dCCA at our centre were retrospectively collected from a prospectively maintained database.Baseline characteristics,NAT type,progression to surgery and oncological outcomes were collected.RESULTS Twelve studies were included.The definition of“unresectable”locally advanced dCCA was heterogenous.Four studies reported outcomes for 9 patients who received NAT for dCCA with extensive vascular involvement.R0 resection rate ranged between 0 and 100%but without survival benefit in most cases.Remaining studies considered either NAT in resectable dCCA or inclusive with extrahepatic CCA.The presented case series includes 9 patients(median age 67,IQR 56-74 years,male:female 5:4)referred for NAT for borderline resectable or locally advanced disease.Three patients progressed to surgery and 2 were resected.One patient died at 14 months with evidence of recurrence at 6 months and the other died at 51 months following recurrence 6 months postoperatively.CONCLUSION Evidence for benefit of NAT is limited.Consensus on criteria for uniform definition of resectability for dCCA is required.We propose using the established National-Comprehensive-Cancer-Network®criteria for pancreatic ductal adenocarcinoma.
文摘BACKGROUND To compare the efficacy and safety of total neoadjuvant therapy(TNT)and neoadjuvant chemoradiotherapy(nCRT)in the treatment of middle and low locally advanced rectal cancer.Our study will systematically collect and integrate studies to evaluate the ability of these two treatments to improve tumor shrinkage rates,surgical resection rates,tumor-free survival,and severe adverse events.AIM To provide clinicians and patients with more reliable treatment options to optimize treatment outcomes and quality of life for patients with locally advanced rectal cancer by comparing the advantages and disadvantages of the two treatment options.METHODS A full search of all clinical studies on the effectiveness and safety of TNT and nCRT for treating locally advanced rectal cancer identified in Chinese(CNKI,Wanfang,China Biomedical Literature Database)and English(PubMed,Embase)databases was performed.Two system assessors independently screened the studies according to the inclusion and exclusion criteria.Quality evaluation and RESULTS Finally,14 studies were included,six of which were randomized controlled studies.A total of 3797 patients were included,including 1865 in the TNT group and 1932 in the nCRT group.The two sets of baseline data were comparable.The results of the meta-analysis showed that the pCR rate[odds ratio(OR)=1.57,95%confidence interval(CI):1.30-1.90,P<0.00001],T stage degradation rate(OR=2.16,95%CI:1.63-2.57,P<0.00001),and R0 resection rate(OR=1.42,95%CI:1.09-1.85,P=0.009)were significantly greater in the nCRT group than in the nCRT group.There was no significant difference in the incidence of grade 3/4 acute toxicity or perioperative complications between the two groups.The 5-year OS[hazard ratio(HR)=0.84,95%CI:0.69-1.02,P=0.08]and DFS(HR=0.94,95%CI:0.03-1.39,P=0.74)of the TNT group were similar to those of the nCRT group.CONCLUSION TNT has greater clinical efficacy and safety than nCRT in the treatment of locally advanced rectal cancer.
基金Supported by Henan Province Medical Science and Technology Tackling Plan Joint Construction Project,No.LHGJ20220684.
文摘BACKGROUND The association between tumor-infiltrating lymphocyte(TIL)levels and the res-ponse to neoadjuvant therapy(NAT)in patients with triple-negative breast cancer(TNBC)remains unclear.AIM To investigate the predictive potential of TIL levels for the response to NAT in TNBC patients.METHODS A systematic search of the National Center for Biotechnology Information PubMed database was performed to collect relevant published literature prior to August 31,2023.The correlation between TIL levels and the NAT pathologic com-plete response(pCR)in TNBC patients was assessed using a systematic review and meta-analysis.Subgroup analysis,sensitivity analysis,and publication bias analysis were also conducted.RESULTS A total of 32 studies were included in this meta-analysis.The overall meta-ana-lysis results indicated that the pCR rate after NAT treatment in TNBC patients in the high TIL subgroup was significantly greater than that in patients in the low TIL subgroup(48.0%vs 27.7%)(risk ratio 2.01;95%confidence interval 1.77-2.29;P<0.001,I2=56%).Subgroup analysis revealed that the between-study hetero-geneity originated from differences in study design,TIL level cutoffs,and study populations.Publication bias could have existed in the included studies.The meta-analysis based on different NAT protocols revealed that all TNBC patients with high levels of TILs had a greater rate of pCR after NAT treatment in all protocols(all P≤0.01),and there was no significant between-protocol difference in the statistics among the different NAT protocols(P=0.29).Additionally,sensitivity analysis demonstrated that the overall results of the meta-analysis remained consistent when the included studies were individually excluded.CONCLUSION TILs can serve as a predictor of the response to NAT treatment in TNBC patients.TNBC patients with high levels of TILs exhibit a greater NAT pCR rate than those with low levels of TILs,and this predictive capability is con-sistent across different NAT regimens.
基金supported by Beijing Science and Technology Innovation Medical Development Foundation (No. KC2021-JF-0167-01 and No. KC2021-JF-0167-24)。
文摘Objective: The aim of this study was to investigate the factors influencing pathological complete response(pCR)rate in early breast cancer patients receiving neoadjuvant dual-target [trastuzumab(H) + pertuzumab(P)] therapy combined with chemotherapy. Additionally, the consistency of the Miller-Payne and residual cancer burden(RCB)systems in evaluating the efficacy of neoadjuvant therapy for early human epidermal growth factor receptor-2(HER2)+ breast cancer was analyzed.Methods: The clinicopathological data of female patients with early-stage HER2+ breast cancer who received dual-target neoadjuvant therapy at 26 hospitals of the Chinese Society of Breast Surgery(CSBrS) from March 2019 to December 2021 were collected. Patients were allocated to four groups: the HER2 immunohistochemistry(IHC)3+/hormone receptor(HR)-, IHC3+/HR+, IHC2+ in situ hybridization(ISH)+/HR-and IHC2+ ISH+/HR+groups. The overall pCR rate for patients, the pCR rate in each group and the factors affecting the pCR rate were analyzed. The consistency between the Miller-Payne and RCB systems in assessing the efficacy of neoadjuvant therapy was analyzed.Results: From March 1, 2019, to December 31, 2021, 77,376 female patients with early-stage breast cancer were treated at 26 hospitals;18,853(24.4%) of these patients were HER2+. After exclusion of unqualified patients, 2,395 patients who received neoadjuvant dual-target(H+P) therapy combined with chemotherapy were included in this study. The overall pCR rate was 53.0%, and the patients' HR statuses and different HER2+ statuses were significantly correlated with the pCR rate(P<0.05). The consistency of the pathological efficacy assessed by the Miller-Payne and RCB systems was 88.0%(κ=0.717, P<0.001).Conclusions: Different HER2 expression statuses and HR expression statuses are correlated with the pCR rate after dual-target neoadjuvant therapy in HER2+ breast cancer patients. There is a relatively good consistency between Miller-Payne and RCB systems in evaluating the pathologic efficacy of neoadjuvant therapy for HER2+breast cancer.
文摘Pancreatic ductal adenocarcinoma(PDAC)remains a significant public health challenge and is currently the fourth leading cause of cancer-related mortality in developed countries.Despite advances in cancer treatment,the 5-year survival rate for patients with PDAC remains less than 5%.In recent years,neoadjuvant therapy(NAT)has emerged as a promising treatment option for many cancer types,including locally advanced PDAC,with the potential to improve patient outcomes.To analyze the role of NAT in the setting of locally advanced PDAC over the past decade,a systematic literature search was conducted using PubMed and Web of Science.The results suggest that NAT may reduce the local mass size,promote tumor downstaging,and increase the likelihood of resection.These findings are supported by the latest evidence-based medical literature and the clinical experience of our center.Despite the potential benefits of NAT,there are still challenges that need to be addressed.One such challenge is the lack of consensus on the optimal timing and duration of NAT.Improved criteria for patient selection are needed to further identify PDAC patients likely to respond to NAT.In conclusion,NAT has emerged as a promising treatment option for locally advanced PDAC.However,further research is needed to optimize its use and to better understand the role of NAT in the management of this challenging disease.With continued advances in cancer treatment,there is hope of improving the outcomes of patients with PDAC in the future.
基金supported by the National Natural Science Foundation of China(Grant No.82203786)the Natural Science Foundation of Liaoning Province of China(Grant No.2022-YGJC-68)Chinese Young Breast Experts Research project(Grant No.CYBER-2021-A02)。
文摘Objective:Neoadjuvant therapy(NAT)has been widely implemented as an essential treatment to improve therapeutic efficacy in patients with locally-advanced cancer to reduce tumor burden and prolong survival,particularly for human epidermal growth receptor 2-positive and triple-negative breast cancer.The role of peripheral immune components in predicting therapeutic responses has received limited attention.Herein we determined the relationship between dynamic changes in peripheral immune indices and therapeutic responses during NAT administration.Methods:Peripheral immune index data were collected from 134 patients before and after NAT.Logistic regression and machine learning algorithms were applied to the feature selection and model construction processes,respectively.Results:Peripheral immune status with a greater number of CD3^(+)T cells before and after NAT,and a greater number of CD8^(+)T cells,fewer CD4^(+)T cells,and fewer NK cells after NAT was significantly related to a pathological complete response(P<0.05).The post-NAT NK cell-to-pre-NAT NK cell ratio was negatively correlated with the response to NAT(HR=0.13,P=0.008).Based on the results of logistic regression,14 reliable features(P<0.05)were selected to construct the machine learning model.The random forest model exhibited the best power to predict efficacy of NAT among 10 machine learning model approaches(AUC=0.733).Conclusions:Statistically significant relationships between several specific immune indices and the efficacy of NAT were revealed.A random forest model based on dynamic changes in peripheral immune indices showed robust performance in predicting NAT efficacy.
基金This study was registered at the Clinical Trial Registration Center Testing Center.The registration identification number is(researchregistry9243).
文摘BACKGROUND Laparoscopic gastrectomy(LG)is widely accepted as a minimally invasive approach for the treatment of early gastric cancer.However,its role in locally advanced gastric cancer(LAGC)after neoadjuvant therapy(NAT)remains controversial.This study aimed to compare the efficacy and safety of LG vs open gastrectomy(OG)after NAT for the treatment of LAGC.AIM To compare the efficacy and safety of LG vs OG after NAT for LAGC.METHODS We conducted a prospective study of 76 patients with LAGC who underwent NAT followed by LG(n=38)or OG(n=38)between 2021 and 2023.The primary endpoint was overall survival(OS),and the secondary endpoints were diseasefree survival(DFS),surgical complications,and quality of life(QOL).RESULTS The two groups had comparable baseline characteristics,with a median follow-up period of 24 mo.The 3-year OS rates in the LG and OG groups were 68.4%and 60.5%,respectively(P=0.42).The 3-year DFS rates in the LG and OG groups were 57.9%and 50.0%,respectively(P=0.51).The LG group had significantly less blood loss(P<0.001),a shorter hospital stay(P<0.001),and a lower incidence of surgical site infection(P=0.04)than the OG group.There were no significant differences in other surgical complications between the groups,including anastomotic leakage,intra-abdominal abscess,or wound dehiscence.The LG group had significantly better QOL scores than the OG group regarding physical functioning,role functioning,global health status,fatigue,pain,appetite loss,and body image at 6 months postoperatively(P<0.05).CONCLUSION LG after NAT is a viable and safe alternative to OG for the treatment of LAGC,with similar survival outcomes and superior short-term recovery and QOL.LG patients had less blood loss,shorter hospitalizations,and a lower incidence of surgical site infections than OG patients.Moreover,the LG group had better QOL scores in multiple domains 6 mo postoperatively.Therefore,LG should be considered a valid option for patients with LAGC who undergo NAT,particularly for those who prioritize postoperative recovery and QOL.
文摘BACKGROUND Colorectal cancer is a common digestive cancer worldwide.As a comprehensive treatment for locally advanced rectal cancer(LARC),neoadjuvant therapy(NT)has been increasingly used as the standard treatment for clinical stage II/III rectal cancer.However,few patients achieve a complete pathological response,and most patients require surgical resection and adjuvant therapy.Therefore,identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance.AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival(OS)and disease-free survival(DFS)for LARC treated with NT.METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017.The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors,which were validated by the Cox regression method.Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves,and that of the two nomograms was conducted by calculating the concordance index(C-index)and calibration curves.The results were validated in a cohort of 65 patients from 2015 to 2017.RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model:Vascular_tumors_bolt,cancer nodules,yN,body mass index,matchmouth distance from the edge,nerve aggression and postoperative carcinoembryonic antigen.The nomogram showed good predictive value for OS,with a C-index of 0.91(95%CI:0.85,0.97)and good calibration.In the validation cohort,the C-index was 0.69(95%CI:0.53,0.84).The risk factor prediction model showed good predictive value.The areas under the curve for 3-and 5-year survival were 0.811 and 0.782.The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77(95%CI:0.69,0.85).In the validation cohort,the C-index was 0.71(95%CI:0.61,0.81).The prediction model for DFS also had good predictive value,with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754.CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.
文摘Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.
基金Supported by Beijing Municipal Science and Technology Project,No.D171100006517004CSCOROCHE Research Fund,No.Y-2019Roche-015
文摘Gastric cancer is one of the most common digestive system tumors in China,and locally advanced gastric cancer(LAGC)accounts for a high proportion of newly diagnosed cases.Although surgery is the main treatment for gastric cancer,surgical excision alone cannot achieve satisfactory outcomes in LAGC patients.Neoadjuvant therapy(NAT)has gradually become the standard treatment for patients with LAGC,and this treatment can not only achieve tumor downstaging and improve surgical rate and the R0 resection rate,but it also significantly improves the long-term prognosis of patients.Peri/preoperative neoadjuvant chemotherapy and preoperative chemoradiotherapy are both recommended according to a large number of studies,and the regimens have also been evolved in the past decades.Since the NCCN guidelines for gastric cancer are one of the most authoritative evidence-based guidelines worldwide,here,we demonstrate the development course and major breakthroughs of NAT for gastric cancer based on the vicissitudes of the NCCN guidelines from 2007 to 2019,and also discuss the future of NAT.
基金Supported by The National 13th Five-Year Science and Technology Plan Major Projects of China,No. 2017ZX10203205-006-001 and No. 2017ZX10203205-001-003。
文摘BACKGROUND The prognosis of intrahepatic cholangiocarcinoma(ICC) with lymph node metastasis is poor.The feasibility of surgery is not certain,which is a contraindication according to the National Comprehensive Cancer Network guidelines.The role of immunotherapy as a neoadjuvant therapy for ICC is not clear.We herein describe a case of ICC with lymph node metastasis that was successfully treated with neoadjuvant therapy.CASE SUMMARY A 60-year-old man with a liver tumor was admitted to our hospital.Enhanced computed tomography and magnetic resonance imaging revealed a spaceoccupying lesion in the right lobe of the liver.Multiple subfoci were found around the tumor,and the right posterior branch of the portal vein was invaded.Liver biopsy indicated poorly differentiated cholangiocytes.According to the American Joint Committee on Cancer disease stage classification,ICC with hilar lymph node metastasis(stage ⅢB) and para-aortic lymph node metastasis was suspected.A report showed that two patients with stage ⅢB ICC achieved a complete response(CR) 13 mo and 16 mo after chemotherapy with a PD-1 monoclonal antibody.After multidisciplinary consultation,the patient was given neoadjuvant therapy,surgical resection and lymph node dissection,and postoperative adjuvant therapy.After three rounds of PD-1 immunotherapy(camrelizumab) and two rounds of gemcitabine combined with cisplatin regimen chemotherapy,the tumor size was reduced.Therefore,a partial response was achieved.Exploratory laparotomy found that the lymph nodes of Group 16 were negative,and the tumor could be surgically removed.Therefore,the patient underwent right hemihepatectomy plus lymph node dissection.The patient received six rounds of chemotherapy and five rounds of PD-1 treatment postoperatively.After 8 mo of follow-up,no recurrence was found,and a CR was achieved.CONCLUSION Neoadjuvant therapy combined with surgical resection is useful for advanced-stage ICC.This is the first report of successful treatment of stage ⅢB ICC using neoadjuvant therapy with a PD-1 inhibitor.
文摘BACKGROUND For locally advanced rectal cancer(LARC),standard therapy[consisting of neoadjuvant chemoradiotherapy(CRT),surgery,and adjuvant chemotherapy(ChT)]achieves excellent local control.Unfortunately,survival is still poor due to distant metastases,which remains the leading cause of death among these patients.In recent years,the concept of total neoadjuvant treatment(TNT)has been developed,whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIM To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODS In a retrospective study,we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT.High-risk for failure was defined according to the presence of at least one of the following factors:T4 stage;N2 stage;positive mesorectal fascia;extramural vascular invasion;positive lateral lymph node.TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin,CRT with capecitabine,and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin prior to surgery.The primary endpoint was pathological complete response(pCR).In total,72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTS Compared to standard therapy,TNT showed a higher proportion of pCR(23%vs 7%;P=0.01),a lower neoadjuvant rectal score(median:8.43 vs 14.98;P<0.05),higher T-and N-downstaging(70%and 94%vs 51%and 86%),equivalent R0 resection(95%vs 93%),shorter time to stoma closure(mean:20 vs 33 wk;P<0.05),higher compliance during systemic ChT(completed all cycles 87%vs 76%;P<0.05),lower proportion of acute toxicity grade≥3 during ChT(3%vs 14%,P<0.05),and equivalent acute toxicity and compliance during CRT and in the postoperative period.The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetricmodulated arc radiotherapy than with 3D conformal radiotherapy(32%vs 9%;P<0.05).CONCLUSION Compared to standard therapy,TNT provides better outcome for LARC patients with high-risk factors for failure,in terms of pCR and neoadjuvant rectal score.
基金supported by Shenzhen Sanming Project(No.SZSM201612051)。
文摘Gastric cancer,with high morbidity and mortality rates,is one of the most heterogeneous tumors.Radical gastrectomy and postoperative chemotherapy are the standard treatments.However,the safety and efficacy of neoadjuvant therapy(NAT)need to be confirmed by many trials before implementation,creating a bottleneck in development.Although clinical benefits of NAT have been observed,a series of problems remain to be solved.Before therapy,more contributing factors should be offered for choice in the intended population and ideal regimens.Enhanced computed tomography(CT)scanning is usually applied to evaluate effectiveness according to Response Evaluation Criteria in Solid Tumors(RECIST),yet CT scanning results sometimes differ from pathological responses.After NAT,the appropriate time for surgery is still empirically defined.Our review aims to discuss the abovementioned issues regarding NAT for GC,including indications,selection of regimens,lesion assessment and NAT-surgery interval time.
基金Supported by National Science Foundation of China,No.81871933and National Science Foundation of China for Youth,No.81802326.
文摘BACKGROUND Neoadjuvant therapy(NAT)is becoming increasingly important in locally advanced rectal cancer.Hence,such research has become a problem.AIM To evaluate the downstaging effect of NAT,its impact on postoperative complications and its prognosis with different medical regimens.METHODS Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy(NRCT)group and the neoadjuvant chemotherapy(NCT)group.The differences between the two groups in tumor regression,postoperative complications,rectal function,disease-free survival,and overall survival were compared using theχ2 test and Kaplan-Meier analysis.RESULTS Baseline data showed no statistical differences between the two groups,whereas the NRCT group had a higher rate of T4(30/55 vs 5/22,P<0.05)than the NCT groups.Twelve cases were evaluated as complete responders,and 15 cases were evaluated as tumor regression grade 0.Except for the reduction rate of T stage(NRCT 37/55 vs NCT 9/22,P<0.05),there was no difference in effectiveness between the two groups.Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage.No significant difference in postoperative complications and disease-free survival between the two groups was observed,although the NRCT group might have better long-term overall survival.CONCLUSION NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor.Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.
基金National Natural Science Foundation of China,No.81772642.
文摘BACKGROUND Laparoscopic total gastrectomy(LTG)has drawn increasing attention over the years.Although LTG has shown surgical benefits compared to open TG(OTG)in early stage gastric cancer(GC),little is known about the surgical and oncological outcomes of LTG for advanced GC following neoadjuvant therapy(NAT).AIM To compare the long-and short-term outcomes of advanced GC patients who underwent LTG vs OTG following NAT.METHODS Advanced GC patients who underwent TG following NAT between April 2011 and May 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences were enrolled and stratified into two groups:LTG and OTG.Propensity score matching analysis was performed at a 1:1 ratio to overcome possible bias.RESULTS In total,185 patients were enrolled(LTG:78;OTG:109).Of these,138 were paired after propensity score matching.After adjustment for propensity score matching,baseline parameters were similar between the two groups.Compared to OTG,LTG was associated with a significantly shorter length of hospital stay(P=0.012).The rates of R0 resection,lymph node harvest,and postoperative morbidity did not significantly differ between the two groups.Overall survival(OS)outcomes were comparable between the two groups.Pathological T and N stages were found to be independent risk factors for OS.CONCLUSION LTG can be a feasible method for advanced GC patients following NAT,as it appears to be associated with better short-and comparable long-term outcomes compared to OTG.
文摘In spite of the high mortality in pancreatic cancer, significant progress is being made. This review discusses multimodality therapy for patients with pancreatic cancer. Surgical therapy currently offers the only potential monomodal cure for pancreatic adenocarcinoma. However only 10%–20% of patients present with tumors that are amenable to resection, and even after resection of localized cancers, long term survival is rare. The addition of chemoradiation therapy significantly increases median survival. To achieve long-term success in treating this disease it is therefore increasingly important to identify effective neoadjuvant/adjuvant multimodality therapies. Preoperative chemoradiation for potentially resectable pancreatic cancer has the following advantages: (1) neoadjuvant treatment would eliminate the delay of adjuvant treatment due to postoperative complications; (2) neoadjuvant treatment could avoid unnecessary surgery for patients with metastatic disease evident on restaging after neoadjuvant therapy; (3) downstaging after neoadjuvant therapy may increase the likelihood for negative surgical margins; and (4) neoadjuvant treatment could prevent peritoneal tumor cell implantation and dissemination caused during surgery. This review systematically summarizes the current status, controversies, and prospects of neoadjuvant treatment of pancreatic cancer.
基金Supported by the National Natural Science Foundation of China,No.81070378 and 81270561Special Research Fund for The First Affiliated Hospital of Chengdu Medical College,No.CYFY2019YB08。
文摘BACKGROUND The number of dissected lymph nodes(LNs)in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIM To investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODS We performed a systematic review and searched Pub Med,Embase(Ovid),MEDLINE(Ovid),Web of Science,and Cochrane Library from January 1,2000 until January 1,2020.Two reviewers examined all the publications independently and extracted the relevant data.Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment(LNs≥12 vs LNs<12).The primary endpoints were the overall survival(OS)and disease-free survival(DFS).RESULTS Nine articles were included in the meta-analyses.Statistical analysis revealed a statistically significant difference in OS[hazard ratio(HR)=0.76,95%confidence interval(CI):0.66-0.88,I2=12.2%,P=0.336],DFS(HR=0.76,95%CI:0.63-0.92,I2=68.4%,P=0.013),and distant recurrence(DR)(HR=0.63,95%CI:0.48-0.93,I2=30.5%,P=0.237)between the LNs≥12 and LNs<12 groups,but local recurrence(HR=0.67,95%CI:0.38-1.16,I2=0%,P=0.348)showed no statistical difference.Moreover,subgroup analysis of LN negative patients revealed a statistically significant difference in DFS(HR=0.67,95%CI:0.52-0.88,I2=0%,P=0.565)between the LNs≥12 and LNs<12 groups.CONCLUSION Although neoadjuvant therapy reduces LN production in rectal cancer,our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’OS,DFS,and DR.
文摘While pancreatic cancer is still characterized by early systemic spread and poor outcomes,the treatment of this disease has changed significantly in recent years due to major advancements in systemic therapy and advanced surgical techniques.Broader use of effective neoadjuvant approaches combined with aggressive surgical operations within a multidisciplinary setting has improved outcomes.Borderline resectable pancreatic cancer is characterized by tumor vascular invasion,and is a setting where the combination of potent neoadjuvant chemotherapy and aggressive surgical methods,including vascular resections and reconstructions,shows its full potential.Hopefully,this will lead to improved local control and curative treatment in a number of patients with this aggressive malignancy.