Failure mode and long-term survival after neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To analyze the fail mode of neoadjuvant therapy combined with surgery for locally advanced esophageal squamous cell carcinoma (ESCC) after long-term follow-up.Methods:Clinical data of consecutive 238 patients with locally advanced resectable ESCC who underwent neoadjuvant therapy combined with surgery in Zhejiang Cancer Hospital from September 2012 to October 2019 were retrospectively analyzed. The failure mode in the whole cohort was analyzed after long-term follow-up. The overall survival (OS) and disease free survival (DFS) rates were analyzed by Kaplan-Meier method. Survival differences were determined by log-rank test.Results:The pathological complete response (pCR) rate was 42.0% in 238 patients. After a median follow-up of 46.1 months, tumor progression occurred in 96 patients (40.3%), including 25 patients (10.5%) with local recurrence, 61 patients (25.6%) with distant metastases, and 10 patients (4.2%) with simultaneous local recurrence and distant metastases. The median OS and DFS were 64.7 months and 49.9 months. And the 3-, 5-, and 7-year OS and DFS rates were 70.0%, 52.8%, 36.4% and 63.5%, 42.5%, and 30.0%, respectively. The 3-, 5-, and 7-year locoregional recurrence-free survival rates and distant metastasis-free survival rates were 86.0%, 71.4%, 61.2% and 70.6%, 55.9%, 43.0%. Compared with non-pCR patients, the overall progression rate and distant metastasis rate of pCR patients were lower (26.0% vs. 50.7%, 16.0% vs. 32.6%, both P<0.05). And the 3-, 5-, and 7-year OS (83.0% vs. 60.2%, 69.7% vs. 41.7%, 50.4% vs. 27.7%, all P<0.001) and DFS rates (80.4% vs. 51.4%, 63.9% vs. 31.2%, 45.9% vs. 20.3%, all P<0.001) were significantly better in pCR patients. Conclusions:Distant metastasis is the main failure mode of patients with locally advanced ESCC after neoadjuvant therapy. Patients with postoperative pCR can achieve better long-term survival.

Research progress on neoadjuvant chemoradiotherapy combined with immunotherapy in locally advanced rectal cancer / 中华放射肿瘤学杂志

For locally advanced (T 3-4/N +M 0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment, which have been demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. Radiotherapy and immunotherapy can supplement each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. These trials have achieved promising short-term efficacy in both microsatellite instability-high (MSI-H) and microsatellite stable (MSS) rectal cancers, which could further improve the rate of tumor response and rate of pathological complete response, increase the possibility of organ preservation and "watch and wait" approach. Large-scale clinical trials need to be performed in the future to demonstrate these findings and to improve long-term prognosis.

Difficulties and strategies of total mesorectal excision for middle and low rectal cancer after neoadjuvant therapy / 中华消化外科杂志

Patients with local advanced rectal cancer (LARC) can benefit from neoadju-vant chemoradiotherapy (nCRT) of reducing local recurrence rate and improving survival rate. However, tissue edema after nCRT may lead to unclear tissue spaces, making it challenging for lymph node dissection and nervous system protection. The difficulty in locating inferior margin of tumor after clinical complete remission or closing to clinical complete remission, as well as the increasing risk of anastomotic leakage after nCRT, pose difficulties and new challenges of total mesorectal excision for middle and low rectal cancer. Based on literatures and clinical experiences, the authors summarize the difficulties and strategies of total mesorectal excision after nCRT, in order to provide reference for colleagues.

Predictors of toxicity after neoadjuvant chemoradiotherapy for locally advanced gall bladder cancer

Background: The present study evaluated the correlation of hepatobiliary toxicity and radiation dose received in patients undergoing neoadjuvant chemoradiotherapy (NACRT) for locally advanced unresectable gall bladder cancers (LAGBC). Methods: Twenty-six patients with LAGBC, treated with NACRT (55–57 Gy/25 fractions/5 weeks and weekly gemcitabine 300 mg/m2) within a phase II study, were included. Whenever feasible, surgery was performed after NACRT. Acute and late hepatobiliary toxicity was recorded. Treatment scans were retrieved to delineate central porto-hepatobiliary system (CPHBS), resected liver surface, segment IV B and V, and duodenum. The doses received by these structures were recorded and correlated with toxicity. Results: Of 26 patients, 20 (77%) had partial or complete response and 12 (46%) had R0 resection. At the median follow-up of 38 months, overall survival was 38%. Eight (30%) patients had post-treatment toxicity, of which most common was biliary toxicity (30%). A correlation was observed between the biliary leak and V45Gy CPHBS >50 cm3 (P = 0.070). Higher toxicity was observed in those with metallic stents (P = 0.072). Conclusion: The incidence of the biliary leak was 46%. CPHBS dose was found to correlate with biliary leaks. Restricting V45Gy CPHBS <50 cm3 and using plastic stent may facilitate a reduction in hepatobiliary toxicity in patients undergoing NACRT and surgery.

Quality of life of patients with locally advanced rectal cancer after neoadjuvant therapy and sphincter-preserving surgery / 中华胃肠外科杂志

Objective: To investigate quality of life (QoL) of patients with locally advanced rectal cancer (LARC) who underwent low anterior resection with protective stoma under neoadjuvant therapy mode, and to explore the changes of QoL of patients from before neoadjuvant therapy to 12 months after stoma reversal. Methods: A descriptive case series study was carried out. A retrospective study was performed on patients with mid and low LARC who received complete neoadjuvant long course radiotherapy and chemotherapy, followed by radical low anterior resection (LAR) combined with protective stoma at Peking Union Medical College Hospital from December 2017 to January 2020. Inclusion criteria: (1) patients with rectal MRI assessment of mT3-4b or mN1-2 without distant metastasis (M0) before neoadjuvant therapy; (2) distance from tumor lower margin to the anal verge <12 cm; (3) rectal adenocarcinoma confirmed by biopsy before neoadjuvant therapy; (4) complete cycle of neoadjuvant therapy; (5) patients undergoing radical LAR with sphincter preservation and protective ostomy; (6) patients receiving follow-up for more than 12 months after stoma reversal. Exclusion criteria: (1) patients as grade Ⅳ to Ⅴclassified by the American Society of Anesthesiologists (ASA); (2) patients with multiple primary colorectal cancer; (3) patients with history of other malignant tumors in the past 5 years; (4) patients of emergency surgery; (5) pregnant or lactating women; (6) patients with history of severe mental illness; (7) patients with contraindication of MRI, radiotherapy, chemotherapy, or surgical treatment. A total of 83 patients were enrolled, including 51 males and 28 females with median age of 59 years and mean BMI of (24.4±3.1) kg/m(2). EORTC QLQ-CR29, international erectile function index (IIEF), Wexner constipation score and low anterior resection syndrome (LARS) score were applied to investigate the QoL of the patients before neoadjuvant therapy, 3 and 12 months after ostomy reversal, including rectal anal function and sexual function. M (P25, P75) was used for the scores of the scale. Results: (1) EORTC QLQ-CR29 score showed that before neoadjuvant therapy, before surgery, 3 months and 12 months after ostomy reversal, anxiety [64.4 (52, 0, 82.5), 75.3 (66.0, 89.5), 82.6 (78.5, 90.0), 83.6 (78.0, 91.0)] and concern about body image [76.8 (66.0, 92.0), 81.1 (76.5, 91.5), 85.5 (82.5, 94.0), 86.1 (82.0, 92.0)] were improved (all P<0.01); pelvic pain [5.4 (2.0, 8.0), 5, 0 (2.0, 7.8), 3.9 (1.0, 5.0), 3.0 (1.0, 5.0)], urinary incontinence [15.7 (7.0, 22.0), 11.1 (0, 17.5), 10.0 (0, 17.0), 9.9 (0, 16.0)], impotence [14.3 (4.2, 19.0), 12.2 (0, 16.8), 5.6 (0, 10.0), 5.2 (0.2, 8.0)], urinate [26.4 (13.0, 38.5), 13.9 (0, 20.0), 13.4 (2.5, 21.5), 13.2 (2.0, 20.0)] and mucous bloody stool [4.7 (3.0, 6.0), 2.6 (0, 5.0), 2.2 (0, 5.0), 1.9 (0, 4.0)] were improved as well (all P<0.01). The scores fluctuated in the improvement of male sexual function, abdominal pain, dry mouth, worry about body mass change, skin pain and dyspareunia, but the symptoms were significantly improved after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). There were no significant changes in female sexual function, dysuria, dysgeusia and fecal incontinence after ostomy reversal compared with before neoadjuvant therapy (all P>0.05). (2) IIEF scale showed that all scores were similar before and after neoadjuvant therapy (all P>0.05). (3) Rectal and anal function scale revealed that before neoadjuvant therapy, before operation, 3 months and 12 months after stoma reversal, gas incontinence [3.1 (0, 4.0), 2.3 (0, 4.0), 1.8 (0, 4.0), 1.2 (0, 3.0)] and urgent defecation [7.2 (0, 11.0), 5.2 (0, 11.0), 2.9 (0, 9.0), 1.7 (0, 0)] were improved (all P<0.001). In terms of improving incomplete emptying sensation, the symptoms fluctuated, but the symptoms improved significantly after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). While the symptoms of assistance with defecation [0 (0, 0), 0.7 (0, 1.0), 0.6 (0, 1.0), 0.7 (0, 1.0)] and defecation failure [0.2 (0, 0), 1.0 (0, 2.0), 0.8 (0, 1.5), 0.8 (0, 1.0)] showed a worsening trend (all P<0.001). Stratified analysis was performed on patients with different efficacy of neoadjuvant therapy to compare the changes in QoL before and after neoadjuvant therapy. Patients with less sensitive and more sensitive neoadjuvant therapy showed similar changes in function and symptoms. Patients with less sensitive therapy showed significant improvement in dysuria, urinary incontinence, skin pain and dyspareunia (all P<0.05), and the symptom of defecation frequency in more sensitive patients was significantly improved (P<0.05). Conclusions: For patients with LARC, neoadjuvant radiochemotherapy combined with radical LAR and protective stoma can improve QoL in many aspects. It is noted that patients show a worsening trend in the need for assistance with defecation and in defecation failure.

A prediction model of pathological complete response in patients with locally advanced rectal cancer after PD-1 antibody combined with total neoadjuvant chemoradiotherapy based on MRI radiomics / 中华胃肠外科杂志

Objective: To construct a prediction model of pathologic complete response (pCR) in locally advanced rectal cancer patients who received programmed cell death protein-1 (PD-1) antibody and total neoadjuvant chemoradiotherapy by using radiomics based on MR imaging data and to investigate its predictive value. Methods: A clinical diagnostic test study was carried out. Clinicopathalogical and radiological data of 38 patients with middle-low rectal cancer who received PD-1 antibody combined with total neoadjuvant chemoradiotherapy and underwent TME surgery from January 2019 to September 2021 in our hospital were retrospectively collected. Among 38 patients, 23 were males and 15 were females with a median age of 68 (47-79) years and 13 (34.2%) a chieved pCR. These 38 patients were stratified and randomly divided into the training group (n=26) and test group (n=12) for modeling. All the patients underwent rectal MRI before treatment. The clinical, imaging and radiomics features of all the patients were collected, and the clinical feature model and radiomics model were constructed. The receiver operating characteristic (ROC) curves of each model were drawn, and the constructed model was evaluated through the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value. Results: There were no significant differences in age, gender, primary location of tumor and postoperative pathology between the two groups (all P>0.05). Forty-one features were extracted from region of interest in each modality, including 9 first-order features, 24 gray level co-occurrence matrix features and 8 shape features. From 38 patients, 41 features were extracted from each imaging modality of baseline and preoperative DWI and T2WI images, totally 164 features. Only 4 features were preserved after correlation analysis between each pair of features and t-test between pCR and non-pCR subjects. After LASSO cross validation, only the first-order skewness of the baseline DWI image before treatment and the volume in the baseline T2WI image before treatment were retained. The area under the curve, sensitivity, specificity, positive and negative predictive values of the prediction model established by applying these two features in the training group and the test group were 0.856 and 0.844, 77.8% and 100.0%, 88.2% and 75.0%, 77.8% and 66.7%, 88.2% and 100.0%, respectively. The decision curve analysis of the radiomics model showed that the strategy of this model in predicting pCR was better than that in treating all the patients as pCR and that in treating all the patients as non-pCR. Conclusion: The pCR prediction model for rectal cancer patients receiving PD-1 antibody combined with total neoadjuvant radiochemotherapy based on MRI radiomics has the potential to be used in clinical screening or rectal cancer patients who can be spared from radical surgery.

Research status and progress on neoadjuvant therapy for esophageal cancer / 中华放射肿瘤学杂志

China is a country with high incidence of esophageal cancer. In recent years, with the deepening research, the value of neoadjuvant therapy in locally advanced resectable esophageal cancer has been widely approved by clinicians, compared with surgery alone or adjuvant therapy. However, the survival results of different neoadjuvant therapy options may be quite different, and many problems remain unresolved. In this article, a systemic literature review was carried out to summarize the radiotherapy target, radiotherapy dose, chemotherapy regimen of neoadjuvant chemoradiotherapy and time to surgery, as well as review the research status and progress on targeted therapy and immunotherapy as neoadjuvant therapy for esophageal cancer.

Influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junction treated by neoadjuvant chemoradio-therapy combined with surgical resection: a prospective study / 中华消化外科杂志

Objective:To investigate the influence of different injection time of carbon nanoparticle tracer on the acquisition of lymph nodes in adenocarcinoma of esophagogastric junc-tion (AEG) treated by neoadjuvant chemoradiotherapy (nCRT) combined with surgical resection.Methods:The prospective randomized controlled study was conducted. The clinicopathological data of 120 AEG patients who were treated by nCRT combined with surgical resection in the Fourth Hospital of Hebei Medical University from March 2020 to March 2021 were selected. Based on random number table, patients were allocated into two groups. Patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before nCRT were allocated into the experiment group, and patients undergoing endoscopic injection of carbon nanoparticle tracer 24 hours before surgical resection were allocated into the control group. All patients received the same plan of nCRT combined with D 2 radical gastrectomy. Observation indicators: (1) grouping situations of the enrolled patients; (2) surgical and postoperative pathological situations; (3) postoperative complications and treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement date with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Results:(1) Grouping situations of the enrolled patients. A total of 120 patients were selected for eligibility. There were 85 males and 35 females, aged (60±9)years. There were 60 patients in the experiment group and 60 patients in the control group, respectively. (2) Surgical and postoperative pathological situations. Patients in the two groups underwent D 2 radical gastrectomy successfully, with R 0 resection. The number of lymph nodes harvest, the number of lymph nodes stained, the number of metastatic lymph nodes stained, the number of micro lymph nodes, the number of inferior mediastinal lymph nodes, the number of inferior mediastinal lymph nodes stained, cases in postoperative pathological stage N0, stage N1, stage N2, stage N3a were 40.6±13.9,20.1±7.7, 1.0(0,3.0), 8.1±2.8, 3.7±1.3, 2.0(1.0,2.0), 18, 13, 23, 6 in patients of the experiment group, respectively. The above indicators were 30.4±8.3, 12.7±3.5, 0(0,1.0), 6.2±2.0, 2.4±1.2, 1.0(0,1.0), 23, 21, 15, 1 in patients of the control group, respectively. There were significant differences in the above indicators between the two groups ( t=-5.01, 6.85, Z=-3.78, t=-4.04, -5.57, Z=-5.48, -2.12, P<0.05). (3) Postoperative complications and treatment. There were 5 cases of the experiment group and 7 cases of the control group with postoperative complications, showing no significant difference between the two groups ( χ2=0.37, P>0.05). The patients with postoperative complications were improved after symptomatic treatment. Conclusion:Compared with injection of carbon nanoparticle tracer 24 hours before surgical resection, injection of carbon nanoparticle tracer 24 hours before nCRT can improve the acquisition of lymph nodes in AEG treated by nCRT combined with surgical resection.

Short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy for locally advanced rectal cancer: a prospective study / 中华消化外科杂志

Objective:To investigate the short-term efficacy of laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-programmed death-1 (PD-1) antibody therapy for locally advanced rectal cancer.Methods:The prospective study was conducted. The clinicopathological data of 30 locally advanced rectal cancer patients who were admitted to the Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from November 2019 to September 2020 were selected. Patients underwent laparos-copic surgery after short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Observation indicators: (1) situations of the enrolled patients; (2) situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events; (3) preoperative evaluation and surgical situations; (4) postoperative situations and pathological examinations; (5) postoperative adjuvant chemo-therapy and follow-up. Follow-up was conducted using outpatient examination and telephone interview up to March 2022. Patients were followed up once every 3 weeks during the period of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy to detect the adverse events and patients were followed up once every 3 months during the first postoperative 2 years and once every 6 months thereafter to detect tumor recurrence and survival of patients. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results:(1) Situations of the enrolled patients. A total of 30 patients were selected for eligibility. There were 17 males and 13 females, aged (57±16)years. Cases with preoperative primary tumor in stage cT3 and cT4 were 22 and 8, respectively. Cases with preoperative clinical lymph node metastasis in stage cN0, cN1, cN2 were 4, 16, 10, respectively. Cases in preoperative clinical stage Ⅱ and Ⅲ were 4 and 26, respectively. Of the 30 patients, there were 21 cases with positive circumferential margin and 12 cases with vascular invasion in extramural of rectum in the preoperative imaging evaluation. Distance from the distal margin of tumor to anal margin and tumor diameter of the 30 patients were 4.7(range, 1.9?9.0)cm and 5.4(range, 2.1?10.0)cm, respectively. There were 28 cases with mismatch repair proficient and 1 case with mismatch repair deficiency in tumor tissues. There was 1 case missing the data of mismatch repair in tumor tissues as failed in biopsy of pathological examination before the treatment. (2) Situations of short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy and adverse events. All the 30 patients completed preoperative short-course radiotherapy successfully. Of the 30 patients, there were 3 cases not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy and there were 24 cases undergoing 2 courses of the sequential chemotherapy combined with anti-PD-1 antibody therapy and 3 cases undergoing 1 course of the sequential chemotherapy combined with anti-PD-1 antibody therapy. The time interval between ending of radiotherapy and starting of chemotherapy combined with anti-PD-1 antibody therapy of the 27 patients was 12(range, 4?18) days. Cases with leukopenia, cases with endothelial hyperplasia of skin capillaries, cases with radiation proctitis, cases with anemia, cases with peripheral neurotoxicity, cases with neutropenia, cases with thrombocytopenia, cases with fatigue, cases with anorexia, cases with abnormal liver function, cases with hypothyroidism were 24, 22, 21,20, 18, 16, 16, 13, 10, 9, 2 in the 30 patients during the preoperative short-course radiotherapy followed by sequential chemotherapy combined with anti-PD-1 antibody therapy. Cases with the above adverse events were improved after symptomatic treatment. (3) Preoperative evaluation and surgical situations. Seven of the 30 patients were in clinical complete remission after preoperative multidisciplinary evaluation and the other 23 patients were not in clinical complete remission. Twenty-seven of the 30 patients underwent laparoscopic radical resection of rectal cancer and 3 patients not undergoing the sequential chemotherapy combined with anti-PD-1 antibody therapy did not undergo surgery. The time interval between ending of chemotherapy combined with anti-PD-1 antibody therapy and the surgery of the 27 patients were 14(range, 5?141)days. Of the 27 cases, there were 13 cases and 14 cases with 0 and 1 of the preoperative Eastern Cooperative Oncology Group score, respectively, and there were 24 cases undergoing low anterior proctectomy and 3 cases undergoing abdominoperineal excision. The operation time and volume of intra-operative blood loss of the 27 cases were (182±36)minutes and 30(range, 10?150)mL, respectively. Of the 27 cases, there were 16 cases with protective ileostomy and 24 cases with anal preservation. (4) Postoperative situations and pathological examinations. The time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay of the 27 patients undergoing surgery were 2(range, 1?4)days, 3(range, 2?5)days and 8(range, 7?16)days, respectively. Five of the 27 patients had postoperative grade Ⅰ?Ⅱ complications, including 2 cases with incision infection, 1 case with abdominal infection, 1 case with incision hemorrhage and 1 case with venous thrombosis in left lower limb intermuscular. Cases with postoperative complica-tions were improved after symptomatic treatment. Results of postoperative pathological examina-tion showed that the rate of pathologic complete response in 27 patients was 48.1%(13/27). Of the 27 cases, cases in grade 0, grade 1, grade 2, grade 3 of the tumor regression grading were 13, 5, 7, 2, respectively, cases in stage T0, stage Tis, stage T2, stage T3 of the tumor T staging were 13, 1, 5, 8, respectively, cases in stage N0, stage N1, stage N2 of the tumor N staging were 19, 6, 2, respectively, cases in stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲ of the tumor TNM staging were 14, 0, 5, 8, respectively. The number of lymph node dissected of the 27 patients was 15(range, 3?29). Of the 27 patients, there was 1 case with positive circumferential margin and 26 cases achieving R 0 resection. None of the 27 patients underwent secondary operation or perioperative death. (5) Postoperative adjuvant chemotherapy and follow-up. Of the 27 patients undergoing surgery, 21 cases underwent post-operative adjuvant chemotherapy, with the cycles of 4(range, 1?6). All the 27 patients were followed up for 20(range, 20?29)months. During the follow-up, 3 cases not achieving pathological complete response had tumor recurrence and no patient died. The disease free survival rate of the 27 patients was 88.9%. Conclusion:Laparoscopic surgery after short-course radiotherapy followed by sequential chemotherapy combined with immunotherapy for locally advanced rectal cancer is safe and feasible, with satisfied short-term efficacy.

Efficacy and safety of total neoadjuvant therapy versus neoadjuvant chemoradiotherapy in the treatment of locally advanced rectal cancer: a meta-analysis / 中华胃肠外科杂志

Objective: To systematically evaluate the efficacy and safety of total neoadjuvant therapy (TNT) in the comprehensive treatment of locally advanced rectal cancer. Methods: Literatures were screened from PubMed, Embase, Web of Science, Cochrane Library, CBM, Wanfang Data, VIP and CNKI from the inception date to May 2021 to collect the randomized controlled clinical trials (RCTs) of TNT followed by total mesorectal excision (TME) versus neoadjuvant chemotherapy (nCRT) followed by TME in the treatment of locally advanced rectal cancer. The data of overall survival, disease-free survival, R0 radical resection rate, pathological complete response (pCR) rate, T downstaging rate, the incidence of adverse events ≥ grade III, including neutropenia, nausea and vomiting, diarrhea, radiation dermatitis and nervous system toxicity, and the morbidity of complications within postoperative 30 days of the two groups were extracted from the included literatures. Review Manager 5.3 software was utilized for statistical meta-analysis. Results: Nine RCTs were finally enrolled including 2430 patients. Meta-analysis results showed that compared with nCRT group, patients in TNT group had longer overall survival (HR=0.80, 95%CI: 0.65-0.97, P=0.03) and higher pCR rate (RR=1.73, 95%CI: 1.44-2.08, P<0.01) with significant differences. Besides, there were no significant differences between two groups in disease-free survival (HR=0.86, 95%CI:0.71-1.05, P=0.14), R0 radical resection rate (RR=1.02, 95%CI: 0.99-1.06, P=0.17) and T downstaging rate (RR=1.04, 95%CI: 0.89-1.22, P=0.58) between two groups. In terms of treatment safety, the incidence of adverse events ≥ grade III (RR=1.09, 95%CI: 0.70-1.70, P=0.70) and morbidity of complications within postoperative 30 days (RR=1.07, 95%CI: 0.97-1.18, P=0.19) did not significantly differ between two groups. Conclusions: In the treatment of locally advanced rectal cancer, TNT may bring more survival benefits than nCRT and does not increase the incidence of adverse events and postoperative complications. Therefore, TNT could be used as a recommended treatment for patients with locally advanced rectal cancer.

Research progress on biomarkers related to the efficacy of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma / 中华放射肿瘤学杂志

Esophageal squamous cell carcinoma is one of the most common malignant tumors in China. Neoadjuvant chemoradiotherapy combined with surgery significantly improved the survival rate of locally advanced operable esophageal squamous cell carcinoma, but approximately half of the patients had poor or no efficacy. To accurately predict the efficacy of neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma and select the dominant population of neoadjuvant chemoradiotherapy, many studies on biomarkers have emerged, which have promoted the progress of neoadjuvant therapy for esophageal squamous cell carcinoma to some extent. In this article, the studies on biomarkers predicting the efficacy of neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma were reviewed.

Genomic prediction of neoadjuvant chemoradiotherapy resistance in rectal cancer / 中华放射肿瘤学杂志

Objective:To search for the key genes influencing the resistance of rectal cancer to chemoradiotherapy based on the weighted gene co-expression network analysis (WGCNA).Methods:The data were collected from gene expression omnibus. The whole genome expression data GSE119409 of patients receiving radiotherapy and chemotherapy were obtained by gene expression ominibus. The weighted gene co-expression networks of pathological complete response group and non-pathological complete response group were constructed respectively. NetRep conservative evaluation method was used to comprehensively analyze the three key network attributes of gene connectivity, gene significance and module membership of each node in the network module, and to determine the key genes closely related to the sensitivity of rectal cancer to radiotherapy and chemotherapy.Results:Network modules including black, blue, green, yellow and purple were obtained by WGCNA, and five key genes including SLC22A14, SIDT2, CABP4, EPHB6 and RAB11B were screened out.Conclusions:Five gene co-expression network modules and five key genes related to chemoradiotherapy resistance of rectal cancer were screened by weighted gene co-expression network analysis, which provided clues for finding molecular markers and potential therapeutic targets for neoadjuvant chemoradiotherapy resistance evaluation.

Correlation analysis between Naples prognostic score and treatment outcomes for locally advanced rectal cancer / 中华放射肿瘤学杂志

Objective:To analyze the correlation between the Naples prognostic score (NPS) after preoperative neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC) and evaluate the prognostic value of NPS in LARC.Methods:136 patients with LARC meeting the recruitment criteria from 2015 to 2020 were selected. Serum albumin, total cholesterol (TC) were collected and neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio were calculated. All patients were scored and graded according to the NPS rule. The survival rate was calculated with Kaplan- Meier method. Multivariate prognostic analysis was performed by Cox models. Results:There was no significant correlation between NPS score and tumor regression or pathological complete response (pCR) of LARC patients after neoadjuvant therapy ( P=0.192, P=0.163). However, Cox multivariate analysis showed that NPS was an independent risk factor for overall survival (OS) and disease-free survival (DFS) of LARC ( P=0.009, P=0.003), and hierarchical analysis suggested that LARC patients with lower NPS score obtained better prognosis. Besides NPS, tumor size was also an independent risk factor for OS, and tumor size and N stage were the independent risk factors for DFS. Conclusion:NPS has no correlation with tumor regression or pCR for LARC after neoadjuvant chemoradiotherapy, whereas it could serve as an effective predictor for long-term prognosis of LARC.

Value of CT radiomics for prediction of pathological response to neoadjuvant chemoradiotherapy in esophageal cancer / 中华放射肿瘤学杂志

Objective:To establish a radiomics-based biomarker for predicting pathological response after preoperative neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal cancer.Methods:From 2008 to 2018, 112 patients with locally advanced esophageal cancer who received nCRT were enrolled. All patients were treated with preoperative nCRT combined with surgery. Enhanced CT images and clinical information before nCRT were collected. A lesion volume of interest was manually delineated. In total, 670 radiomics features (including tumor intensity, shape and size, texture and wavelet characteristics) were extracted using the pyradiomics package in PYTHON. The stepwise regression combined with the best subset were employed to select the features, and finally the Logistic regression model was adopted to establish the prediction model. The performance of the classifier was evaluated by the area under the ROC curve (AUC). Results:The pathological complete remission (pCR) rate was 58.0%(65/112). 10 radiomics features were included in the final model, The most relevant radiomics feature was the gray feature (the texture information of the image), followed by the shape and voxel intensity-related features. In the training set, the AUC was 0.750 with a sensitivity of 0.711 and a specificity of 0.778, the corresponding values in the testing set were 0.870, 0.757 and 0.900, respectively.Conclusions:Models based on radiomics features from CT images can be utilized to predict the pathological response to nCRT in esophageal cancer. As it is efficient, non-invasive and economic model, it could serve as a promising tool for individualized treatment when validated by further prospective trials in the future.

Research progress on prediction methods for esophageal cancer response to neoadjuvant chemoradiotherapy / 中华放射肿瘤学杂志

The incidence of esophageal cancer ranks third among all malignant tumors in China. Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for locally advanced esophageal cancer. Whether the tumor lesions can achieve complete pathological remission after neoadjuvant chemoradiotherapy provide profound guidance for subsequent treatment. In this article, research progresses on the application of pathological, radiological and biological approaches to evaluate and predict the tumor response to neoadjuvant chemoradiotherapy were reviewed.

Comparison of efficacy and safety between neoadjuvant chemoradiotherapy followed by surgery and immediate surgery in the treatment of resectable and borderline resectable pancreatic cancer: a Meta-analysis / 中华放射肿瘤学杂志

Objective:To systematically evaluate the efficacy and safety between neoadjuvant chemoradiotherapy followed by surgery and immediate surgery in the treatment of resectable and borderline resectable pancreatic cancer.Methods:Literature review was performed from PubMed, Embase, Cochrane Library, Web of Science, CBM, Wanfang, CNKI and VIP from the inception date to February, 2020 using the key words including "pancreatic neoplasm, pancreatic cancer, surgery, preoperative chemoradiotherapy, neoadjuvant chemoradiotherapy" in both English and Chinese. The randomized controlled clinical trials (RCTs) of neoadjuvant chemoradiotherapy followed by surgery versus immediate surgery in the treatment of resectable and borderline resectable pancreatic cancer were searches. Literature screening, data extraction and estimation of the risk of bias were independently conducted by two researchers. The HR and 95% CI were used for estimating the overall survival time. The R 0 resection rate, overall incidence of postoperative complications, and mortality rate throughout treatment were assessed by the RR and 95% CI. The heterogeneity of the studies was analyzed using the I2 test. Results:A total of 4 RCTs were included. Among 400 patients, 197 cases were assigned into the neoadjuvant chemoradiotherapy combined with surgery group and 203 in the immediate surgery group. The results of Meta-analysis showed that patients in the neoadjuvant chemoradiotherapy followed by surgery group obtained longer overall survival ( HR=0.76, 95% CI: 0.60-0.97, P=0.03) and higher R 0 resection rate ( RR=1.72, 95% CI: 1.40-2.13, P<0.01). Besides, the overall incidence of postoperative complications ( RR=1.02, 95% CI: 0.73-1.43, P=0.90) and mortality rate throughout treatment ( RR=1.19, 95% CI: 0.48-2.93, P=0.71) did not significantly differ between two groups. Conclusions:During the treatment of resectable or borderline resectable pancreatic cancer, neoadjuvant chemoradiotherapy followed by surgery may bring more survival benefits than immediate surgery and does not increase the incidence of postoperative complications and mortality rate throughout treatment. Therefore, neoadjuvant chemoradiotherapy followed by surgery can be used as a recommended treatment for patients with resectable or borderline resectable pancreatic cancer.

MRI differences between locally advanced rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma before and after neoadjuvant chemoradiotherapy / 中华放射学杂志

Objective:To investigate the MRI differences between locally advanced rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma before and after neoadjuvant chemoradiotherapy (NCR).Methods:A retrospective cohort study was conducted to collect the clinical and imaging data of 165 patients with locally advanced rectal adenocarcinoma treated by NCR combined with surgery from October 2016 to October 2019 in the Sixth Affiliated Hospital of Sun Yat-sen University, 36 cases were rectal mucinous adenocarcinoma and 129 cases were non-mucinous adenocarcinoma. The image features of the two groups before and after NCR were evaluated based on MRI, including the length and thickness of the tumor, the distance from the lower edge of the tumor to the anal edge, T stage, N stage, involvement of mesorectal fascia (MRF) and peritoneal reflux. The difference of NCR and the change of MRI characteristics after NCR were compared by independent sample t test, Mann-Whitney U test or χ 2 test. The accuracy of MRI re-staging after NCR was evaluated according by postoperative pathological staging results. Results:Before NCR, there was significant difference in length of tumor between mucinous adenocarcinoma and non-mucinous adenocarcinoma groups ( P=0.044), there was no significant difference in the distance from the lower edge of the tumor to the anal edge, thickness of the tumor, T stage, N stage, involvement of MRF and peritoneal reflux (all P>0.05). After NCR, in patients with non-mucinous adenocarcinoma, the distance reduction from the lower edge of the tumor to the anal edge, the length reduction of the tumor, the thickness reduction of the tumor, the T-stage decline rate were significantly higher than those in the mucinous adenocarcinoma group (all P<0.05). The N-stage decline rate of mucinous adenocarcinoma was higher than that in non-mucinous adenocarcinoma group ( P=0.008). After NCR, MRI overestimated T staging of patients with both mucinous adenocarcinoma and non-mucinous adenocarcinoma compared with pathological T-stage ( P<0.001). In patients with mucinous adenocarcinoma, MRI overstated the N-stage than pothology ( P=0.001). Conclusions:There is different sensitivity of mucinous adenocarcinoma and non-mucinous adenocarcinoma to NCR. Patients with non-mucinous adenocarcinoma benefit more from the efficacy of NCR. The accuracy of MRI in re-staging of rectal mucinous adenocarcinoma and non-mucinous adenocarcinoma after NCR needs to be improved.

Analysis of clinical factors influencing the effect of neoadjuvant chemoradiotherapy for locally advanced rectal cancer / 中国综合临床

Objective:To investigate the clinical factors influencing the efficacy and prognosis of neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC).Methods:The clinical data of 335 patients with LARC who underwent radical operation after nCRT in Liaoning Cancer Hospital were retrospectively analyzed.Through univariate and multivariate analysis, we found out the clinical factors that may affect the efficacy and prognosis of nCRT in patients with LARC.Results:Multivariate logistic regression analysis showed that the independent clinical factors influencing the curative effect of nCRT in LARC patients were tumor invasion circumference( OR=2.350, 95% CI: 1.438-3.842, P=0.01), cT stage( OR=2.101, 95% CI: 1.024-4.314, P=0.043) and cN stage( OR=5.836, 95% CI: 3.305-10.306, P<0.01). Competitive risk model analysis showed that the independent factors affecting the prognosis of LARC patients were tumor regression grading (TRG) ( HR=3.236, 95% CI: 1.714-6.110, P<0.01), cT stage ( HR=1.852, 95% CI: 1.061-3.230, P=0.030), cN stage ( HR=2.008, 95% CI: 1.083-0.372, P=0.027), and carcinoembryonic antigen (CEA) level before nCRT ( HR=7.038, P<0.01), 95% CI: 3.894-12.720, P<0.01) and serum carbohydrate antigen 199 (CA199) ( HR=3.849, 95% CI: 2.016-7.350, P<0.01). Conclusion:The larger the circumference of tumor invasion before nCRT, cT stage and the cN stage were independent clinical factors influencing the nCRT efficacy of LARC patients.The larger the degree of tumor invasion to the rectum, the higher cT stage and the higher the cN stage before nCRT, the worse the efficacy of nCRT in LARC patients may be. TRG grade, cT stage, cN stage, CEA and CA199 level before nCRT were independent factors affecting the prognosis of LARC patients who received nCRT. The higher the TRG grade, of LARC patients receiving nCRT, the higher cT and cN stage, and the higher the CEA and CA199 level before nCRT, the worse the prognosis of LARC patients may be.

Diagnosis and treatment of lateral lymph node metastasis in 4K laparoscopic surgery for middle and low rectal cancer / 中华消化外科杂志

Lateral lymph node metastasis (LLNM) is one of the major causes for post-operative local recurrence of middle and low rectal cancer. At present, there are still controversies on the diagnosis and treatment of LLNM. The radiological assessment of LLNM generally relies on morphological criteria such as the size or shape of the node or the response to therapy, in which the diagnostic accuracy of MRI is superior to that of other imaging techniques. Neoadjuvant chemoradiotherapy could not achieve good local control for suspicious LLNM. Lateral lymph node dissection (LLND) can reduce tumor local recurrence significantly, but the clinical value of LLND in survival and quality of life of patients has been questioned. 4K laparoscope can decrease the incidence of perioperative complications and urinary and sexual dysfunction to a certain extent. Thus, selective LLND should be undertaken to patients with suspicious LLNM after neoadjuvant chemoradiotherapy, in order to reduce tumor local recurrence and improve the prognosis of patients. The authors elaborate on diagnosis and treatment including surgery or chemoradiotherapy of LLNM in 4K laparoscopic surgery for middle and low rectal cancer combined with their own experiences.

Current situation and think of watch and wait strategy after neoadjuvant treatment of rectal cancer / 国际外科学杂志

Some patients with rectal cancer can achieve clinical complete response (cCR) after neoadjuvant chemoradiotherapy. The watch and wait strategy for cCR patients can achieve similar curative effects as radical surgery, avoid surgical complications, and significantly improve the quality of life of patients, which is attracting increasing attention. Although the existing research results support that the watch and wait strategy is safe and feasible, there is still a lack of high-level evidence-based medicine evidence. There are still many issues in the implementation of the watch and wait strategy that need to be further clarified, including long-term oncology efficacy, cCR diagnosis and evaluation criteria, appropriate patient selection, follow-up strategies during the observation period, and treatment methods for local tumor regeneration. This article will explain the above problems based on the results of the existing literature and the clinical experience of our center.