| Objective:Neoadjuvant chemoradiotherapy(nCRT)plus surgery has been a standard treatment for locally advanced esophageal cancer or carcinoma of the gastroesophageal junction(EC/GEJ).At present,the recommended preoperative radiation dose ranges from 41.4 to 50.4 Gy,but an optimal preoperative radiation dose is still unclear.We performed this systematic review to explore the treatment efficacy and safety of different radiation dose levels and find an optimal dose-fractionation strategy in EC/GEJ patients receiving nCRT.Methods:Relevant studies were searched from Ovid Medline and Embase using EMTREE,keyword as well as free-word term searches.The final literature search was performed on July 05,2019.Physical dose distributions were converted to biologically equivalent dose(BED)which was described in the unit of Gy(alpha/beta)where the alpha/beta ratio used was 10.BED≤48.85 Gy10 was considered as low-dose radiotherapy(LDRT)and BED>48.85 Gy10 was defined as high-dose radiotherapy(HDRT).Pooled rates of R0 resection,pCR,PFS,OS,failure patterns,adverse events and postoperative complications between LDRT group and HDRT group were calculated by R studio.The efficacy and safety of different dose-fractionation strategies were further explored.Results:A total of 110 studies with 7577 EC/GEJ patients receiving nCRT were included in this pooled analysis.Among them,3910 patients received LDRT and 3667 patients received HDRT.The pooled analysis indicated that(1).The 1-、2-,3-and 5-year pooled PFS rates were 71.1%,54.3%,47.5%and 41.2%respectively in LDRT group and 64.8%,47.5%,38.9%and 32.1%respectively in HDRT group.The 1-,2-,3-and 5-year pooled OS rates were 78.9%,57.7%,50.9%and 39.0%respectively in LDRT group and 74.7%,53.3%,42.8%and 34.4%respectively in HDRT group.Both PFS and OS rates of patients who received LDRT were significantly higher than those who received HDRT(P<0.05).(2).The incidence rates of>3 grade adverse events in the LDRT group were significantly lower than in the HDRT group except for mucositis.Patients who received LDRT also had significantly lower distant failure rates than patients who received HDRT(P<0.05).(3).The utilization of modern RT techniques could further bring improved survival as compared with conventional RT techniques.For patients receiving modern RT techniques,the 1-,2-,3-and 5-year pooled OS rates were 84.6%,68.8%,58.7%and 48.5%respectively in LDRT group and 79.2%,58.5%,47.6%and 41.1%respectively in HDRT group.Patients receiving LDRT had significantly superiority of OS rates.(4).For patients receiving modern RT techniques,subgroup analysis showed that patients who received a conventionally fractionated regimen with a total dose of 40.0-41.4Gy showed a better survival rate than those who received 44.0-50.4Gy.The 1-,2-,3-and 5-year pooled OS rates were 84.4%,68.6%,58.5%and 48.5%respectively in patients receiving 40.0-41.4Gy group;79.5%,52.8%,44.9%and 40.9%respectively in 44.0-46.0Gy group and 81.5%,66.1%,52.6%and 43.8%respectively in 50.0-50.4Gy group.(6).For ESCC patients receiving modern RT techniques,the 1-,2-,3-and 5-year pooled OS rates were 86.9%,73.2%,61.7%and 49.1%respectively in 40.0-41.4Gy group and 79.4%,61.2%,54.9%and 50.0%respectively in 44.0-50.4Gy group.Patients receiving 40,0-41.4Gy had superior survival as compared with 44.0-50.4Gy radiation.(6).Sensitivity analysis showed that,when CROSS trial,NEOCRTEC5010 trial and studies with high risk of bias were excluded,LDRT group again showed the significant superiority of OS rates.Conclusions:nCRT using BED≤48.85Gy10 was suitable for locally advanced resectable EC/GEJ patients.A total dose of 40.0-41.4Gy in 20-23 fractions might be an optimal option for ocally advanced resectable EC/GEJ patients.Objective:To investigate the efficacy and safety of neoadjuvant therapy for locally advanced esophageal cancer.Methods:From January 2018 to January 2021,40 patients with locally advanced esophageal cancer who received neoadjuvant therapy in Clinical Medical College of Yangzhou University and Affiliated Hospital of Yangzhou University underwent neoadjuvant therapy followed by esophagectomy.General clinical data of patients were collected.The short-term efficacy,toxicity,R0 resection rate,pathologic complete response(pCR)rate and postoperative complications were evaluated by imaging,pathological and hematological results before and after treatment.Result:40 patients received neoadjuvant therapy and surgery.The patients characteristics were as follows:The median age was 65 year;male/female:30/10;squamous cell carcinoma/adenocarcinoma/poorly differentiated carcinoma:28/1/1;upper-middle/middle/middle-lower/lower:5/5/19/11;cStage Ⅰ/Ⅱ/Ⅲ:2/19/19;35 patients received neoadjuvant chemotherapy(nCT).Among them,21 patients received chemotherapy consisted of paclitaxel-liposome+cisplatin/nedaplatin;9 patients received chemotherapy consisted of paclitaxel+cisplatin/nedaplatin;2 patients received chemotherapy consisted of nanoparticle albumin-bound paclitaxel+nedaplatin;the other 3 patients received chemotherapy consisted of docetaxel+cisplatin,docetaxel+oxaliplatin+tegafur and raltitrexed+cisplatin,respectively.5 patients received neoadjuvant chemoradiotherapy(nCRT).Among them,3 patients received chemotherapy consisted of paclitaxel+cisplatin;the other 2 patients received chemotherapy consisted of paclitaxel-liposome+nedaplatin and albumin-bound paclitaxel+cisplatin,respectively.Patients receiving nCRT were treated with intensity-modulated radiation therapy(IMRT),the median dose was 45Gy(range 40-46Gy).The short-term efficacy and safety of neoadjuvant therapy:The lesions of 36 patients could be evaluated.No patients received complete response(CR),partial response(PR)in 17 patients,stable disease(SD)in 18 patients,and progressive disease(PD)in 1 patient.The objective response rate(ORR)as 47.2%and the disease control rate(DCR)was 97.2%.No treatment-related deaths were observed.Grade 3 hematotoxicities were anemia:1 patient;leukopenia:9 patients;neutropenia:8 patients.3 patients occurred grade 4 neutropenia.No grade 3/4 hepatotoxicity or nephrotoxicity was observed.Postoperative staging and safety:All 40 patients underwent surgical resection.Post-surgery stage was Ⅰ/Ⅱ/Ⅲ/ⅣA:10/10/13/3;The R0 resection rate was 100%and pCR rate was 10%(4/40).In nCT group,1 patient achieved pCR(1/35).In nCRT group,3 patients achieved pCR(3/5).Postoperative complications were anastomotic leak:3 patients;anastomotic stenosis:2 patients;pulmonary infection:4 patients;pleural effusion:5 patients;respiratory failure:2 patients.No patients died within 30 days after surgery.Conclusion:Neoadjuvant therapy is effective in the treatment of locally advanced esophageal cancer,with tolerable toxicity and high surgical resection rate.The pCR rate of nCRT was higher than that of nCT,which is worthy of clinical application. |
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