Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of debate.AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database Article.Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected.RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival.The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than nCRT.Moreover,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for LAEC.However,nCT exhibited better performance in terms of postoperative complications.

Compare clinical efficacy and safety of neoadjuvant therapy and neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Meta-analysis

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.

Effect of postoperative adjuvant chemotherapyon the prognosis of patients with ypT0-3N0 rectalcancer undergoing neoadjuvant chemoradiotherapy

Objective The aim of this study was to investigate the effect of adjuvant chemotherapy (AC) on theprognosis of patients with ypT0-3N0 rectal cancer undergoing neoadjuvant chemoradiotherapy.Methods The study participants were 110 patients with locally advanced rectal cancer. Thirty-fourpatients did not receive postoperative AC treatment, and the other 76 patients received postoperative ACtreatment. The differences in the 5-year overall survival (OS) and disease-free survival (DFS) between thetwo groups were compared.Results Age was an important determinant of the patients’ decision to undergo postoperative treatment.Patients who did not receive AC treatment were significantly older than those who received AC treatment(P < 0.05). The tumor location (distance above anal margin) in the AC group was significantly larger thanthat in the non-AC group (P < 0.05). Moreover, there was no significant difference in the 5-year DFS andOS between the two groups. Postoperative AC did not significantly improve the prognosis of patients withrectal cancer. Age, tumor differentiation, and the number of resected lymph nodes were independent factorsaffecting the OS of patients (P < 0.05). Older patients, patients with lower degree of tumor differentiation,and patients with <12 resected lymph nodes showed worse prognosis (P < 0.05).Conclusion Patients with rectal cancer whose ypT0-3N0 stage is reduced after neoadjuvantchemoradiotherapy, especially those without adverse prognostic factors, do not need AC after surgery.

Neoadjuvant chemoradiotherapy for resectable esophageal carcinoma:A meta-analysis

AIM:To compare neoadjuvant chemoradiotherapy and surgery with surgery alone for resectable esophageal carcinoma. METHODS:We used MEDLINE and EMBASE databases to identify eligible studies and manual searches were done to ensure no studies were missed.Trial validity assessment was performed and a trial quality score was assigned. RESULTS:Eleven randomized controlled trials(RCTs) including 1308 patients were selected.Neoadjuvant chemoradiotherapy significantly improved the overall survival compared with surgery alone.Odds ratio(OR) [95%confidence interval(CI),P value],expressed as neoadjuvant chemoradiotherapy and surgery vs surgery alone,was 1.28(1.01-1.64,P=0.05)for 1-year survival,1.78(1.20-2.66,P=0.004)for 3-year survival,and 1.46(1.07-1.99,P=0.02)for 5-year survival.Postoperative mortality increased in patients treated by neoadjuvant chemoradiotherapy(OR: 1.68,95%CI:1.03-2.73,P=0.04),but incidence of postoperative complications was similar in two groups (OR:1.14,95%CI:0.88-1.49,P=0.32).Neoadjuvant chemoradiotherapy lowered the local-regional cancer recurrence(OR:0.64,95%CI:0.41-0.99,P=0.04), but incidence of distant cancer recurrence was similar (OR:0.94,95%CI:0.68-1.31,P=0.73).Histological subgroup analysis indicated that esophageal squamous cell carcinoma did not benefit from neoadjuvantchemoradiotherapy,OR(95%CI,P value)was 1.16(0.85-1.57,P=0.34)for 1-year survival,1.34 (0.98-1.82,P=0.07)for 3-year survival and 1.41 (0.98-2.02,P=0.06)for 5-year survival. CONCLUSION:Neoadjuvant chemoradiotherapy can raise the survival rate of patients with esophageal adenocarcinoma.

Long-term outcomes in patients with ypT0 rectal cancer after neoadjuvant chemoradiotherapy and curative resection

Objective： For patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy（NCRT）, significant pathological response of the primary tumor has been proposed to identify candidates for organ preservation. However, this does not address metastatic lymph nodes in the mesorectum. The aim of this study was to assess the incidence of lymph node metastases in ypT0 patients treated with NCRT and curative resection and to explore risk factors associated with survival.Methods： This was a retrospective study of patients with ypT0 rectal cancer after NCRT and curative resection at a tertiary care center in China from 2005 to 2014.Results： A total of 60（18.6%） patients who underwent surgery after NCRT and achieved ypT0 were enrolled in this study; one patient was excluded owing to lack of follow-up. Of these 59 patients, lymph node metastases were found in the mesorectum（ypT0N＋） in eight（13.6%） patients. After a median follow-up of 52 months, 5-year recurrence-free survival（82.7% vs. 62.5%, P=0.014） and overall survival（OS）（90.9% vs. 70.0%, P=0.032） were much higher in ypN0 than yp N＋ patients. Multivariate analyses showed that ypN＋ status（P=0.009） and perioperative blood transfusion（BT）（P=0.001） were significantly independent risk factors associated with recurrence; however, no factor was correlated with 5-year OS.Conclusions： Patients with ypT0N0 rectal cancer can achieve excellent long-term outcomes; however, positive lymph nodes or tumor deposits can still be found in 13.6% of ypT0 patients. Nodal positivity in the mesorectum and perioperative BT are independent risk factors for recurrence.

Neoadjuvant chemoradiotherapy plus surgery in the treatment of potentially resectable thoracic esophageal squamous cell carcinoma

BACKGROUNDIn recent years, neoadjuvant chemoradiotherapy (NCRT) combined with surgeryhas been gradually applied in patients with locally advanced thoracic esophagealcancer, but its effectiveness and safety remains unclear. In this clinical trial, weprospectively investigated the efficacy and safety of NCRT plus surgery in thetreatment of thoracic esophageal squamous cell carcinoma (TESCC).AIMTo investigate the efficacy and safety of NCRT combined with surgery in thetreatment of potentially resectable TESCC.METHODSThirty patients with advanced TESCC hospitalized in our hospital from July2016 to June 2019 were prospectively studied. All patients received NCRT, whichincluded intensity modulated conformal radiotherapy (40-44 Gy/20-22f, 2 Gy/f)and chemotherapy (paclitaxel 150-175 mg/m2d1, 22 + lobaplatin 25-30 mg/m2d2,23 for two cycles). Surgery was performed after radiotherapy and chemotherapy.The effectiveness and safety of these treatments were observed.RESULTSAmong these 30 patients, complete response was achieved in two cases (6.7%) andpartial response in 26 cases (86.7%), yielding an objective response rate of 100%.All patients underwent radical surgery successfully. The R0 resection rate was100%, and the pathologic complete response rate was 33.3%. The incidence ofgrade III- IV granulocytopenia was 10% during the NCRT, and anastomoticleakage occurred in one patient after surgery.CONCLUSIONFor patients with potentially resectable TESCC, NCRT can effectively reduce thetumor size, increase R0 resection rate, and achieve obvious pathologicaldegradation, with mild adverse reactions. Thus, it is worthy of wider clinicalapplication.

Predictive factors for early distant metastasis after neoadjuvant chemoradiotherapy in locally advanced rectal cancer

BACKGROUND Distant relapse is the leading cause of cancer-related death in locally advanced rectal cancer.Neoadjuvant chemoradiation(NACRT)followed by surgery inevitably delays delivery of systemic treatment.Some patients show early distant metastasis before systemic treatment.AIM To identify the most effective treatments.We investigated prognostic factors for distant metastasis,especially early distant metastasis,using the standard treatment paradigm to identify the most effective treatments according to recurrence risk.METHODS From January 2015 through December 2019,rectal cancer patients who underwent NACRT for having clinical T 3-4 or clinical N 1-2 disease according to the 8th American Joint Committee on Cancer staging system were included.Radiotherapy was delivered to the whole pelvis with concomitant chemotherapy.Patients received surgery 6-8 wk after completion of NACRT.Adjuvant chemotherapy was administered at the physician’s discretion.RESULTS A total of 127 patients received NACRT.Ninety-three patients(73.2%)underwent surgery.The R0 resection rate was 89.2%in all patients.Pathologic tumor and node downstaging rates were 41.9%and 76.3%.Half the patients(n=69)received adjuvant chemotherapy after surgery.The 3-year distant metastasis-free survival(DMFS)and overall survival(OS)rates were 81.7%and 83.5%.On univariate analyses,poorly differentiated tumors,>5 cm,involvement of mesorectal fascia(MRF),or presence of extramural involvement(EMVI)were associated with worse DMFS and OS.Five patients showed distant metastasis at their first evaluation after NACRT.Patients with early distant metastasis were more likely to have poorly differentiated tumor(P=0.025),tumors with involved MRF(P=0.002),and EMVI(P=0.012)than those who did not.CONCLUSION EMVI,the involvement of MRF,and poor histologic grade were associated with early distant metastasis.In order to control distant metastasis and improve treatment outcome,selective use of neoadjuvant treatment according to individualized risk factors is necessary.Future studies are required to determine effective treatment strategies for patients at high risk for distant metastasis.

Predictive value of a serum tumor biomarkers scoring system for clinical stage Ⅱ/Ⅲ rectal cancer with neoadjuvant chemoradiotherapy

BACKGROUND Multiple classes of molecular biomarkers have been studied as potential predictors for rectal cancer(RC)response.Carcinoembryonic antigen(CEA)is the most widely used blood-based marker of RC and has proven to be an effective predictive marker.Cancer antigen 19-9(CA19-9)is another tumor biomarker used for RC diagnosis and postoperative monitoring,as well as monitoring of the therapeutic effect.Using a panel of tumor markers for RC outcome prediction is a practical approach.AIM To assess the predictive effect of pre-neoadjuvant chemoradiotherapy(NCRT)CEA and CA19-9 levels on the prognosis of stage II/III RC patients.METHODS CEA and CA19-9 levels were evaluated 1 wk before NCRT.According to the receiver operating characteristic curve analysis,the optimal cut-off point of CEA and CA19-9 levels for the prognosis were 3.55 and 19.01,respectively.The novel serum tumor biomarker(NSTB)scores were as follows:score 0:Pre-NCRT CEA<3.55 and CA19-9<19.01;score 2:Pre-NCRT CEA>3.55 and CA19-9>19.01;score 1:Other situations.Pathological information was recorded according to histopathological reports after the operation.RESULTS In the univariate analysis,pre-NCRT CEA<3.55[P=0.025 for overall survival(OS),P=0.019 for disease-free survival(DFS)],pre-NCRT CA19-9<19.01(P=0.014 for OS,P=0.009 for DFS),a lower NSTB score(0-1 vs 2,P=0.009 for OS,P=0.005 for DFS)could predict a better prognosis.However,in the multivariate analysis,only a lower NSTB score(0-1 vs 2;for OS,HR=0.485,95%CI:0.251-0.940,P=0.032;for DFS,HR=0.453,95%CI:0.234-0.877,P=0.019)and higher pathological grade,node and metastasis stage(0-I vs II-III;for OS,HR=0.363,95%CI:0.158-0.837,P=0.017;for DFS,HR=0.342,95%CI:0.149-0.786,P=0.012)were independent predictive factors.CONCLUSION The combination of post-NCRT CEA and CA19-9 was a predictive factor for clinical stage II/III RC patients receiving NCRT,and the combined index had a stronger predictive effect.

Effect of Weight Loss on Survival in Esophageal Cancer Patients undergoing Neoadjuvant Chemoradiotherapy and Surgery

Objective This study aimed to determine the impact of weight loss during neoadjuvant chemoradiotherapy on the survival of patients with esophageal carcinoma.Methods We retrospectively examined 102 consecutive patients with esophageal carcinoma who underwent neoadjuvant chemoradiotherapy followed by radical resection at Sichuan Cancer Hospital&Institute between 2003 and 2017.The patients were divided into three groups based on the amount of body weight lost during neoadjuvant chemoradiotherapy:severe weight loss(>10%),high weight loss(5%~10%),and low weight loss(<5%).The correlations of weight loss with toxicity,progressionfree survival,and overall survival were investigated.Results The median overall survival was 49.7 months in the low weight loss group compared with 35.4 and 25.1 months in the high and severe weight loss groups(P=0.041).The 1-year overall survival rates in the severe,high,and low weight loss groups were 62.5%,85.0%,and 90.7%,respectively;the corresponding 3-year overall survival rates were 21.9%,47.3%,and 68.8%,respectively,and the corresponding 5-year overall survival rates were 21.9%,31.0%,and 44.4%,respectively.The multivariate analysis indicated that a pathological complete response and severe weight loss were independent prognostic factors for overall survival.Any leukopenia(P=0.024),leukopenia of at least grade 3(P=0.021),and anemia(P=0.042)occurred more frequently in the severe weight loss group.Conclusions Weight loss during neoadjuvant CRT is an independent and adverse prognostic factor in esophageal carcinoma patients,whereas a stable weight confers a better prognosis.

Timing of surgery after neoadjuvant chemoradiotherapy affects oncologic outcomes in patients with esophageal cancer

BACKGROUND The optimal time interval between neoadjuvant chemoradiotherapy(nCRT)and esophagectomy in esophageal cancer has not been defined.AIM To evaluate whether a prolonged time interval between the end of nCRT and surgery has an effect on survival outcome in esophageal cancer patients.METHODS We searched PubMed,Embase,Web of Science,the Cochrane Library,Wanfang and China National Knowledge Infrastructure databases for relevant articles published before November 16,2019,to identify potential studies that evaluated the prognostic role of different time intervals between nCRT and surgery in esophageal cancer.The hazard ratios and 95%confidence intervals(95%CI)were merged to estimate the correlation between the time intervals and survival outcomes in esophageal cancer,esophageal squamous cell carcinoma and adenocarcinoma using fixed-and random-effect models.RESULTS This meta-analysis included 12621 patients from 16 studies.The results demonstrated that esophageal cancer patients with a prolonged time interval between the end of nCRT and surgery had significantly worse overall survival(OS)[hazard ratio(HR):1.107,95%CI:1.014-1.208,P=0.023]than those with a shorter time interval.Subgroup analysis showed that poor OS with a prolonged interval was observed based on both the sample size and HRs.There was also significant association between a prolonged time interval and decreased OS in Asian,but not Caucasian patients.In addition,a longer wait time indicated worse OS(HR:1.385,95%CI:1.186-1.616,P<0.001)in patients with adenocarcinoma.CONCLUSION A prolonged time interval from the completion of nCRT to surgery is associated with a significant decrease in OS.Thus,esophagectomy should be performed within 7-8 wk after nCRT.

Neoadjuvant chemoradiotherapy followed by laparoscopic distal gastrectomy in advanced gastric cancer: A case report and review of literature

BACKGROUND The laparoscopic technique has been widely applied for early gastric cancer,with the advantages of minimal invasion and quick recovery.However,there is no report about the safety and oncological outcome of laparoscopic gastrectomy with D2 lymph node dissection for patients after neoadjuvant chemoradiotherapy.CASE SUMMARY A 60-year-old man was diagnosed with advanced distal gastric cancer,cT4aN1M0 stage III.The neoadjuvant chemoradiotherapy was performed based on the regimen of gross tumor volume 50G y/25 f and clinical target volume 45 Gy/25 f,as well as concurrent S-160 mg Bid.Then laparoscopic distal gastrectomy with D2 lymph node dissection was undertaken successfully for him after achieving partial response evaluated by radiological examination.The patient recovered smoothly without moderate or severe postoperative complications.The postoperative pathological stage was ypT3N0M0 with American Joint Committee on Cancer tumor regression grade 1.He was still in good condition after 5 years of follow-up.CONCLUSION Neoadjuvant chemoradiotherapy followed by laparoscopic technique could be applicable and may achieve satisfactory oncological outcomes.Our finding requires further validation by cohort studies.

Neoadjuvant chemoradiotherapy for locally advanced gastric cancer with bulky lymph node metastasis:Five case reports

BACKGROUND Neoadjuvant chemoradiotherapy(NACRT)has not been accepted as a general therapy for gastric cancer because of its localized effect and toxicity for radiosensitive organs.However,if radiation therapy could compensate for the limited or inadequate treatment choices available for elderly patients and/or those at high risk,the available therapeutic options for advanced gastric cancer might increase.From this perspective,we present our experiences of five patients with advanced gastric cancer in whom we used NACRT therapy with interesting results.CASE SUMMARY We admitted five patients with clinical Stage III gastric cancer and bulky lymph node metastasis or adjacent organ invasion at the time of diagnosis.A total of 50 Gy of preoperative intensity modulated radiation therapy was delivered to the patients in doses of 2.0 Gy/d,together with a regimen of concomitant chemotherapy comprising two courses of oral tegafur/gimeracil/oteracil(S-1;65 mg/m2 per day)for three consecutive weeks followed by two weeks of rest,starting at the same time as radiotherapy.All patients underwent no residual tumor resection and a pathological complete response of the primary tumors was achieved in two patients.The incidence of hematological toxicity was low,although the digestive toxicities of anorexia and diarrhea developed in three of the five patients,necessitating termination of radiation therapy at 30 Gy and S-1 at three weeks.However,even 30 Gy of irradiation and half the dose of S-1 resulted in sufficient downstaging,indicating that even a reduced amount of NACRT could confer considerable effects.CONCLUSION Slightly reduced NACRT might be useful and safe for patients with locally advanced gastric cancer.

Predictive value of indirect bilirubin before neoadjuvant chemoradiotherapy in evaluating prognosis of local advanced rectal cancer patients

BACKGROUND Many biomarkers have predictive value for overall survival(OS)and disease-free survival(DFS)in tumor patients.However,the role of indirect bilirubin(IBIL)in local advanced rectal cancer(LARC)patients treated with neoadjuvant chemoradiotherapy(nCRT)has not been studied.AIM To explore the predictive value of IBIL before nCRT(pre-IBIL)for the OS and DFS of LARC patients treated with nCRT.METHODS A total of 324 LARC patients undergoing nCRT with total mesorectal excision(TME)were enrolled.Preoperative clinical features and postoperative pathological characteristics were collected.Cox regression analysis was performed,and a Cox-based nomogram was developed to predict OS and DFS.We also assessed the predictive performance of the nomogram with calibration plots and receiver operating characteristic(ROC)curves.RESULTS Among 324 patients,the median pre-IBIL was 6.2μmol/L(interquartile range:4.6μmol/L-8.4μmol/L).In the Cox multivariate regression analysis,we found that pre-IBIL,smoking history,tumor regression grade(TRG),vascular invasion,and carbohydrate antigen 19-9 before nCRT(pre-CA19-9)were predictors of OS.Additionally,pre-IBIL,body mass index(BMI),nCRT with surgery interval,TRG,and vascular invasion were predictors of DFS.Predictive nomograms were developed to predict 5-year OS and 5-year DFS with area under the ROC curve values of 0.7518 and 0.7355,respectively.Good statistical performance on internal validation was shown by calibration plots and ROC curves.CONCLUSION This study demonstrated that pre-IBIL was an independent prognostic factor for OS and DFS in LARC patients treated with nCRT followed by TME.Nomograms incorporating pre-IBIL,BMI,smoking history,nCRT with surgery interval,TRG,vascular invasion,and pre-CA19-9 could be helpful to predict OS and DFS.

Consolidation chemotherapy with capecitabine after neoadjuvant chemoradiotherapy in high-risk patients with locally advanced rectal cancer:Propensity score study

BACKGROUND The effects of consolidation chemotherapy(CC) in neoadjuvant therapy in locally advanced rectal cancer(LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy(NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear.AIM To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval.METHODS We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm(c T3c-c T3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC(capecitabine 1000 mg/m^(2) twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching(PSM) and inverse probability of treatment weight(IPTW) were used to balance the differences between the two groups. The main outcome was the complete response(CR) rate.RESULTS A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d(range, 37-168). The CR rate was 24.3% and 16.3%(P = 0.107) in the CC and non-CC groups’ original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group(27.6% vs 16.2%, P = 0.045;25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo(range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples(73.2% vs 71.9%, P = 0.913;92.3% vs 86.7%, P = 0.294), PSM(73.2% vs 73.5%, P = 0.865;92.5% vs 89.3%, P = 0.612), and IPTW(73.8% vs 72.1%, P = 0.913;92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups(49.3% vs 53.5%, P = 0.492).CONCLUSION One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in highrisk LARC but failed to improve the long-term outcomes.

CEA levels predict tumor response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Objective The aim of this study was to evaluate the impact of serum carcinoembryonic antigen(CEA)in the prediction of pathological complete response(pCR)in locally advanced rectal cancer(LARC)patients treated with neoadjuvant chemoradiotherapy(nCRT).Methods A total of 925 LARC patients who underwent nCRT followed by TME between March 2006 and February 2018 were enrolled at Fudan University Shanghai Cancer Center.Using logistic regression models,we investigated the associations between serum CEA levels and pathological complete remission(pCR).Further stratified analyses were performed according to different CEA thresholds.Results We found that pre-nCRT CEA and post-nCRT CEA were negatively correlated with pCR(P<0.001).Stratified analyses revealed that when the CEA cutoff value was set to 5 ng/mL,10.6%of patients with post-nCRT CEA levels>5 ng/mL achieved pCR.Meanwhile,when the CEA cutoff value was set to 10 ng/mL,only 6.8%of the patients with post-nCRT CEA levels>10 ng/mL achieved pCR.Conclusion In summary,pre and post-nCRT CEA levels≤5 ng/mL were favorable predictors of pCR in LACR patients,and the“watch and wait”strategy is not recommended for patients with post-nCRT CEA levels>10 ng/mL.

Neoadjuvant chemoradiotherapy for resectable esophageal cancer:an in-depth study of randomized controlled trials and literature review

Surgery following neoadjuvant chemoradiotherapy(NCRT) is a common multidisciplinary treatment for resectable esophageal cancer(EC). After analyzing 12 randomized controlled trials(RCTs), we discuss the key issues of surgery in the management of resectable EC. Along with chemoradiotherapy, NCRT is recommended for patients with squamous cell carcinoma(SCC) and adenocarcinoma(AC), and most chemotherapy regimens are based on cisplatin, fluorouracil(FU), or both(CF). However, taxane-based schedules or additional studies, together with newer chemotherapies, are warranted. In nine clinical trials, post-operative complications were similar without significant differences between two treatment groups. In-hospital mortality was significantly different in only 1 out of 10 trials. Half of the randomized trials that compare NCRT with surgery in EC demonstrate an increase in overall survival or disease-free survival. NCRT offers a great opportunity for margin negative resection, decreased disease stage, and improved loco-regional control. However, NCRT does not affect the quality of life when combined with esophagectomy. Future trials should focus on the identification of optimum regimens and selection of patients who are most likely to benefit from specific treatment options.

Endoscopic ultrasound-guided injection of carbon nanoparticles suspension to label rectal cancer before neoadjuvant chemoradiotherapy:a retrospective cohort study

Background:Localization of the primary tumor and ensuring safe distal surgical margins(DSMs)following neoadjuvant chemoradiotherapy(nCRT)are challenging in locally advanced rectal cancers(LARCs).This study investigated the effectiveness of carbon nanoparticles suspension(CNS)for labeling the primary tumor and allowing precise tumor resection after nCRT.Methods:Clinicopathological data of LARC patients who underwent nCRT followed by laparoscopic radical anal preservation surgery at our center between January 2018 and February 2023 were prospectively collected.The patients were divided into the CNS tattooed(CNS)and non-tattooed(control)groups.In the CNS group,CNS was injected in four quadrants on the anal side 1 cm away from the lower tumor margin.DSMs were determined through intraoperative distal rectal examination in the control group and observation of CNS tattoos in the CNS group.DSM lengths and positive DSM rates were compared between the two groups to analyse the feasibility and effectiveness of CNS for labeling LARCs before nCRT.Results:There was no statistically significant difference in the basic demographic data,effectiveness of nCRT,or post-operative recovery rates between the two groups(all P>0.05).In the CNS group,CNS tattoos were observed on the outside of the rectal wall,with an overall efficiency of 87.1%(27/31).The CNS group had fewer positive DSMs and safer DSM lengths(2.73±0.88 vs 2.12±1.15 cm,P=0.012)than the control group(P<0.05).Conclusions:Endoscopic ultrasound-guided injection of CNS tattoos before nCRT could effectively label the LARCs,ensuring safe DSMs during anus-preserving surgeries(Chictr.org.cn No.:ChiCTR2300068991).

“Watch and wait”strategy after neoadjuvant chemoradiotherapy in rectal cancer:opportunities and challenges

The"watch and wait"(W&W)strategy has been widely used in rectal cancer patients who have achieved clinical complete response(cCR)after neoadjuvant chemoradiotherapy(nCRT),which can save them from surgery and improve their quality of life.However,this strategy also has many unsolved practical problems,including the improvement of cCR/pCR rate,the search for efficient predictors,the standard follow-up and the methods of rescue surgery,etc.Larger sample size and more standardized clinical trials are still needed to obtain credible evidence.Therefore,we must rationally view the cCR after nCRT for middle and low rectal cancer,understand the risk of W&W strategy,and make a reasonable choice.It is particularly important to emphasize that we should actively carry out prospective multi-center clinical trials to produce high-level evidence suitable for Chinese characteristics,so that more rectal cancer patients can benefit from nCRT.

Radiation-induced injury on surgical margins:a clue to anastomotic leakage after rectal-cancer resection with neoadjuvant chemoradiotherapy?

Background:Few studies on anastomotic condition after rectal-cancer resection and its effect on anastomotic leakage(AL)are available up to now.This study aimed to investigate potential radiation-induced injury left on surgical margins of anterior resection after neoadjuvant chemoradiotherapy(nCRT)and its association with AL.Methods:We retrospectively identified 161 consecutive patients who underwent anterior resection with nCRT,neoadjuvant chemotherapy without radiation(nCT)or no neoadjuvant therapy between 2014 and 2015.Tissue samples of resection margins were assessed using a specific histopathological score and microvessel density in submucosa.Propensity score matching was used to balance the baseline characteristics.Association between AL and histopathological features was analysed.Results:AL occurred in 13 of 54 patients undergoing nCRT,5 of 48 patients undergoing nCT and 7 of 59 patients without neoadjuvant therapy.Comparisons after matching showed median(range)histopathological scores as follows:3(0–8)vs 0(0–3)vs 0(0–2)for the proximal margin(P<0.001);4(2–9)vs 0(0–4)vs 0(0–3)for the distal margin(P<0.001).Correspondingly,mean(SD)microvessel densities were as follows:21.7(7.9)vs 27.2(8.6)vs 27.3(9.4)for the proximal margin(P=0.003);18.1(9.3)vs 25.2(12.9)vs 24.9(7.4)for the distal margin(P<0.001).Among patients undergoing nCRT,AL was associated with increased histopathological score(P=0.003)and decreased microvessel density(P=0.004)on the proximal margin.Conclusions:Surgical margins of rectal-cancer resection are exposed to certain radiation-induced injury after nCRT.AL is associated with aggravated radiation damage on the proximal margin.

Impact of neoadjuvant chemoradiotherapy on the local recurrence and distant metastasis pattern of locally advanced rectal cancer: a propensity score-matched analysis

Background:Previous studies have demonstrated different predominant sites of distant metastasis between patients with and without neoadjuvant chemoradiotherapy(NCRT).This study aimed to explore whether NCRT could influence the metastasis pattern of rectal cancer through a propensity score-matched analysis.Methods:In total,1296 patients with NCRT or post-operative chemoradiotherapy(PCRT)were enrolled in this study between January 2008 and December 2015.Propensity score matching was used to correct for differences in baseline characteristics between the two groups.After propensity score matching,the metastasis pattern,including metastasis sites and timing,was compared and analyzed.Results:After propensity score matching,there were 408 patients in the PCRT group and 245 patients in the NCRT group.NCRT significantly reduced local recurrence(4.1%vs.10.3%,P=0.004),but not distant metastases(28.2%vs.27.9%,P=0.924)compared with PCRT.In both the NCRT and PCRT groups,the most common metastasis site was the lung,followed by the liver.The NCRT group developed local recurrence and distant metastases later than the PCRT group(median time:29.2[18.8,52.0]months vs.18.7[13.3,30.0]months,Z=–2.342,P=0.019;and 21.2[12.2,33.8]vs.16.4[9.3,27.9]months,Z=–1.765,P=0.035,respectively).The distant metastases occurred mainly in the 2nd year after surgery in both the PCRT group(39/114,34.2%)and NCRT group(21/69,30.4%).However,20.3%(14/69)of the distant metastases appeared in the 3rd year in the NCRT group,while this number was only 13.2%(15/114)in the PCRT group.Conclusions:The predominant site of distant metastases was the lung,followed by the liver,for both the NCRT group and PCRT group.NCRT did not influence the predominant site of distant metastases,but the NCRT group developed local recurrence and distant metastases later than the PCRT group.The follow-up strategy for patients with NCRT should be adjusted and a longer intensive follow-up is needed.