Ki-67 Change in Anthracyline-containing Neoadjuvant Chemotherapy Response in Breast Cancer

Objective Anthracycline-containing regimens are irreplaceable in neoadjuvant chemotherapy(NAC)for breast cancer(BC)at present.However,30% of early breast cancer(EBC)patients are resistant to anthracycline-containing chemotherapy,leading to poor prognosis and higher mortality.Ki-67 is associated with the prognosis and response to therapy,and it changes after NAC.Methods A total of 105 BC patients who received anthracycline-containing NAC were enrolled.Then,the optimal model of Ki-67 was selected,and its predictive efficacy was analyzed.Immunohistochemistry(IHC)was used to determine the estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER-2)status and Ki-67 level.Fluorescent in situ hybridization(FISH)was used to verify the HER-2 when the IHC score was 2+.Results The post-NAC Ki67 level after treatment with anthracycline drugs was lower than pre-NAC Ki-67(19.6%±23.3%vs.45.6%±23.1%,P<0.001).Furthermore,patients with the Ki-67 decrease had a border line higher pathological complete response(pCR)rate(17.2%vs.0.0%,P=0.068),and a higher overall response rate(ORR)(73.6%vs.27.8%,P<0.001),when compared to patients without the Ki-67 decrease.The ΔKi-67 and ΔKi-67%were valuable markers for the prediction of both the pCR rate and ORR.The area under the curve(AUC)for ΔKi-67 on pCR and ORR was 0.809(0.698-0.921)and 0.755(0.655-0.855),respectively,while the AUC for ΔKi-67% on pCR and ORR was 0.857(0.742-0.972)and 0.720(0.618-0.822),respectively.Multivariate logistic regression model 1 revealed thatΔKi-67 was an independent predictor for both pCR[odds ratio(OR)=61.030,95% confidence interval(CI)=4.709-790.965;P=0.002]and ORR(OR=10.001,95%CI:3.044-32.858;P<0.001).Multivariate logistic regression model 2 revealed thatΔKi-67%was also an independent predictor for both pCR(OR=408.922,95%CI=8.908-18771.224;P=0.002)and ORR(OR=5.419,95%CI=1.842-15.943;P=0.002).Conclusions The present study results suggest thatΔKi67 andΔKi67%are candidate predictors for anthracycline-containing NAC response,and that they may provide various information for further systematic therapy after surgery in clinical practice.

Development of a novel staging classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction after neoadjuvant chemotherapy

BACKGROUND Stage classification for Siewert Ⅱ adenocarcinoma of the esophagogastric junction(AEG)treated with neoadjuvant chemotherapy(NAC)has not been established.AIM To investigate the optimal stage classification for Siewert Ⅱ AEG with NAC.METHODS A nomogram was established based on Cox regression model that analyzed variables associated with overall survival(OS)and disease-specific survival(DSS).The nomogram performance in terms of discrimination and calibration ability was evaluated using the likelihood-ratio test,Akaike information criterion,Harrell concordance index,time-receiver operating characteristic curve,and decision curve analysis.RESULTS Data from 725 patients with Siewert type Ⅱ AEG who underwent neoadjuvant therapy and gastrectomy were obtained from the Surveillance,Epidemiology,and End Results database.Univariate and multivariate analyses revealed that sex,marital status,race,ypT stage,and ypN stage were independent prognostic factors of OS,whereas sex,race,ypT stage,and ypN stage were independent prognostic factors for DSS.These factors were incorporated into the OS and DSS nomograms.Our novel nomogram model performed better in terms of OS and DSS prediction compared to the 8th American Joint Committee of Cancer pathological staging system for esophageal and gastric cancer.Finally,a user-friendly web application was developed for clinical use.CONCLUSION The nomogram established specifically for patients with Siewert type Ⅱ AEG receiving NAC demonstrated good prognostic performance.Validation using external data is warranted before its widespread clinical application.

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.

Correlation and predictive value of pathological complete response and ultrasound characteristic parameters in neoadjuvant chemotherapy for breast

BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for patients.AIM To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022.According to the Miller-Payne grading system,the pathological response,i.e.efficacy,of the NAC in the initial breast lesion after NAC was evaluated.Of these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches.RESULTS In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(P<0.05).The area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,respectively.Also,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictive value for NAC efficacy,they are significantly associated with poor response to NAC in breast cancer patients.

Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial issue.AIM To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving NAC.METHODS The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December 2020.Least absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to NAC.RESULTS In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 years.According to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was 0.806.The calibration curve revealed that the predicted value exhibited good agreement with the actual value.Decision curve analysis showed that the nomogram had a good value in clinical application.CONCLUSION A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

Post-operative morbidity after neoadjuvant chemotherapy and resection for gallbladder cancer: A national surgical quality improvement program analysis

BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.

Evaluation of the efficacy of neoadjuvant chemotherapy for intermediate and advanced breast cancer by 3.0T MR and ultrasound combined with tumour markers

Objective:To evaluate the efficacy of neoadjuvant chemotherapy before and after neoadjuvant chemotherapy for intermediate and advanced breast cancer using 3.0T MR and ultrasound in combination with tumour markers(CEA,CA-153,CA125),and to provide therapeutic references for the clinicians,so as to better satisfy the needs of treatment for intermediate and advanced breast cancer patients.Methods:The team collected 30 patients who were diagnosed with intermediate and advanced breast cancer by biopsy and received neoadjuvant chemotherapy,and divided them into sensitive and insensitive groups according to the MP grading of postoperative pathological results.The team retrospectively analysed the changes in the values of serum CEA,CA-153,and CA 125 before and after the neoadjuvant chemotherapy,the changes in the average ADC of the lesions before and after the observation by MRI,and the changes in the volume and size of lesions before and after the observation by ultrasonography to assess the effects of neoadjuvant chemotherapy individually,and the results of neoadjuvant chemotherapy were evaluated individually.The effect of neoadjuvant chemotherapy was assessed independently.Each of the above was evaluated independently,and the accuracy of each item was calculated by comparing the evaluation results with the pathological examination results,and the accuracy of the single item was compared with the accuracy of the three combined tests to determine whether the combined evaluation was more consistent.Results:All three examination and testing methods can achieve high accuracy,and the combined evaluation of the three is more accurate than the evaluation of the single way,and the difference is statistically significant(P<0.05).Conclusion:In neoadjuvant chemotherapy for breast cancer patients,the combined assessment of MR,CDFI and tumour markers can more comprehensively and accurately assess the effect of ADC,and more accurately guide the clinical treatment and determine the prognosis.

Application Progress of Ultrasound Radiomics in the Evaluation and Prediction of Neoadjuvant Chemotherapy for Breast Cancer

Breast cancer is a malignant tumor with the highest incidence in women. In recent years, the incidence of breast cancer has shown an increasing trend, especially in younger patients, which seriously threatens the life and health of women. In order to improve the treatment effect of breast cancer, neoadjuvant chemotherapy has become a reliable strategy to cooperate with surgical treatment and improve the prognosis of advanced breast cancer, which is conducive to quickly and accurately curbing the growth of cancer cells, controlling the patients’ condition, reducing their pain, and improving the cure rate of breast cancer patients. This paper analyzes the development history of ultrasound radiomics, explores its application in the evaluation and prediction of neoadjuvant chemotherapy for breast cancer, and clarifies the research results of multimodal ultrasound radiomics in the analysis of high-order characteristics of breast cancer tumors and the evaluation of tumor heterogeneity, so as to provide references for the clinical treatment of breast cancer.

Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer:protocol for a prospective,double-arm,randomized controlled clinical trial

Background:Neoadjuvant chemotherapy plays a vital role in the treatment of advanced gastric cancer(GC),however,optimizing its effectiveness remains an important research focus.Traditional Chinese medicine(TCM),a promising adjunctive therapy,has shown enhanced clinical outcomes when combined with postoperative adjuvant chemotherapy.Therefore,this study is designed to evaluate the clinical efficacy of Yiqi Huayu Jiedu decoction combined with neoadjuvant chemotherapy FLOT in the treatment of advanced GC.Methods:This study is a prospective,double-arm,randomized controlled trial.It involves a total of 260 patients diagnosed with advanced GC,who will be randomly assigned to two groups-a TCM treatment group and a control group,each comprising 130 patients.All patients will receive standard FLOT chemotherapy,and patients in the TCM treatment group will additionally receive TCM treatment with Yiqi Huayu Jiedu decoction.After four cycles of chemotherapy,GC D2 radical surgery will be performed.The primary objective is to evaluate the postoperative pathological response rate of the tumor.The secondary objectives include evaluating the perioperative nutritional status,the efficacy of TCM syndrome,and adverse events associated with both chemotherapy and surgery.Discussion:Currently,no trials have investigated the impact of TCM in combination with neoadjuvant chemotherapy on the preoperative treatment in patients with advanced GC.Accordingly,it is imperative to conduct this prospective study to evaluate the clinical efficacy and safety of this regimen,meanwhile providing high-level clinical evidence for TCM combined with neoadjuvant chemotherapy and introducing an innovative regimen for preoperative comprehensive treatment of GC.

Current Status and Research Progress of Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer

Gastric cancer is one of the most common malignant tumours worldwide, with a high degree of malignancy and a poor prognosis. While early gastric cancer can be cured by surgical treatment, locally advanced gastric cancer requires neoadjuvant therapy to shrink the tumour, suppress potential metastases, achieve down-staging, and provide patients with the opportunity for radical surgery to prolong their survival. This article reviews the current status and progress of neoadjuvant chemotherapy for locally advanced gastric cancer.

Value of Pretreatment Inflammation-nutrition Score to Predict Non-response to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer

Objective To investigate the value of pretreatment inflammatory-nutritional biomarkers in predicting the pathological response of locally advanced rectal cancer(LARC)after neoadjuvant chemotherapy(nCT).Methods This retrospective study included eligible participants who underwent nCT followed by radical surgery.Pretreatment inflammatory nutritional biomarkers were calculated within one week prior to nCT.Correlations between biomarkers and pathological responses were analyzed.The cut-off values of the pretreatment biomarkers for predicting non-response were determined using receiver operating characteristic(ROC)curve analysis.The inflammation-nutrition score was calculated using the lymphocyte level,neutrophil-to-lymphocyte ratio(NLR),and prognostic nutritional index(PNI).Results A total of 235 patients were retrospectively recruited between January 2017 and September 2022.Lower lymphocyte levels,lymphocyte monocyte ratio(LMR),and PNI,and higher NLR and platelet-to-lymphocyte ratio(PLR)were observed in patients without response.Multivariate logistic regression analysis revealed that NLR could independently predict non-response to nCT in patients with LARC.The sensitivity and specificity of the inflammation-nutrition score for predicting nonresponse were 71.2%and 61.7%,respectively.Conclusion The pretreatment inflammation-nutrition score is a practical parameter for predicting nonresponse to nCT in patients with LARC.Patients with high scores were more likely to respond poorly to nCT.

Comparison between upfront surgery and neoadjuvant chemotherapy in patients with locally advanced gastric cancer:A systematic review

BACKGROUND Gastric cancer(GC)is a major health concern worldwide.Surgical resection and chemotherapy is the mainstay treatment for gastric carcinoma,however,the optimal approach remains unclear and should be different in each individual.Chemotherapy can be administered both pre-and postoperatively,but a multidisciplinary approach is preferred when possible.This is particularly relevant for locally advanced GC(LAGC),as neoadjuvant chemotherapy(NAT)could potentially lead to tumor downsizing thus allowing for a complete resection with curative intent.Even though the recent progress has been impressive,European and International guidelines are still controversial,thus attenuating the need for a more standardized approach in the management of locally advanced cancer.AIM To investigate the effects of NAT on the overall survival(OS),the disease-free survival(DFS),the morbidity and the mortality of patients with LAGC in comparison to upfront surgery(US).METHODS For this systematic review,a literature search was conducted between November and February 2023 in PubMed,Cochrane Library and clinicaltrials.gov for studies including patients with LAGC.Two independent reviewers conducted the research and extracted the data according to predetermined inclusion and exclusion criteria.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to form the search strategy and the study protocol has been registered in the International Prospective Register of Systematic Reviews.RESULTS Eighteen studies with 4839 patients with LAGC in total were included in our systematic review.Patients were separated into two groups;one receiving NAT before the gastrectomy(NAT group)and the other undergoing upfront surgery(US group).The OS ranged from 41.6%to 74.2%in the NAT group and from 30.9%to 74%in the US group.The DFS was also longer in the NAT group and reached up to 80%in certain patients.The complications related to the chemotherapy or the surgery ranged from 6.4%to 38.1%in the NAT group and from 5%to 40.5%in the US group.Even though in most of the studies the morbidity was lower in the NAT group,a general conclusion could not be drawn as it seems to depend on multiple factors.Finally,regarding the mortality,the reported rate was higher and up to 5.3%in the US group.CONCLUSION NAT could be beneficial for patients with LAGC as it leads to better OS and DFS than the US approach with the same or even lower complication rates.However,patients with different clinicopathological features respond differently to chemotherapy,therefore currently the treatment plan should be individualized in order to achieve optimal results.

Prognostic Impact of Histopathologic Response after Neoadjuvant Chemotherapy in Stage Ⅲ_A Non-small Cell Lung Cancer

Objective： To investigate prognostic impact of histopathologic response induced by neoadjuvant chemotherapy in patients with stage ⅢA non-small cell lung cancer （NSCLC）. Methods： Forty patients with stage ⅢA NSCLC underwent two cycles of neoadjuvant chemotherapy with mitomycin, vindosine, and cisplatin followed by surgery. Histopathologic response in resection of the tumor was examined after surgery. Tumor regression was classified as grade Ⅳ, grade Ⅲ, grade Ⅱ, and grade Ⅰ according to the extent of tumor necrosis and the extent of the vital tumor tissues. The tumor regression grading was correlated with the survival time of the patients. Results： After two cycles of chemotherapy, 19 （47.5%） of 40 patients had objective response （2 complete and 17 partial response）. In 40 resected tumor specimens, 2 （5%） were classified as regression grade Ⅳ, 16 （40%） as regression grade Ⅲ, 18 （45%） as regression gradeⅡ, and 4 （10%） as regression grade Ⅰ. The rate of complete surgical resection was significantly higher in patients with tumor regression grade Ⅲ-Ⅳ （〈10% vital tumor tissue）（P〈0.05）. The median survival time in patients classified as having tumor regression grade Ⅲ-Ⅳ was significantly longer than that in patients who had regression grade Ⅰ-Ⅱ （P〈0.05）. The 3-year survival rate in patients with regression grade Ⅲ-Ⅳ was markedly higher than that in patients who had regression grade Ⅰ-Ⅱ （P〈0.05）. Conclusion： The extent of tumor regression induced by neoadjuvant chemotherapy is a critical issue for successful therapeutic approach in patients with stage ⅢA NSCLC. In resected specimens of tumors after chemotherapy, the presence of marked tumor regression （regression grade Ⅲ-Ⅳ） is predictive for superior survival time.

Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer

AIM:To investigate feasibility,morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer.METHODS:Patients suffering from locally-advanced(T3-4 any N M0 or any T N1-3 M0)gastric carcinoma,staged with endoscopic ultrasound,bone scan,computed tomography,and laparoscopy,were assigned to receive four 21 d/cycles of TCF(docetaxel 75 mg/m 2 day 1,cisplatin 75 mg/m 2 day 1,and fluorouracil 300 mg/m 2 per day for days 1-14),either before(Arm A)or after(Arm B)gastrectomy.Operative morbidity,overall mortality,and severe adverse events were compared by intention-to-treat analysis.RESULTS:From November 1999 to November 2005,70 patients were treated.After preoperative TCF(Arm A),thirty-two(94%)resections were performed,85% of which were R0.Pathological response was complete in 4 patients(11.7%),and partial in 18(55%).No surgical mortality and 28.5%morbidity rate were observed,similar to those of immediate surgery arm(P= 0.86).Serious chemotherapy adverse events tended to be more frequent in arm B(23%vs 11%,P=0.07),with a single death per arm.CONCLUSION:Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma.

Neoadjuvant chemotherapy for advanced gastric cancer:A meta-analysis

AIM:To study the value of neoadjuvant chemotherapy (NAC) for advanced gastric cancer by performing a meta-analysis of the published studies.METHODS:All published controlled trials of NAC for advanced gastric cancer vs no therapy before surgery were searched.Studies that included patients with metastases at enrollment were excluded.Databases included Cochrane Library of Clinical Comparative Trials,MEDLINE,Embase,and American Society of Clinical Oncology meeting abstracts from 1978 to 2010.The censor date was up to April 2010.Primary outcome was the odds ratio (OR) for improving overall survival rate of patients with advanced gastric cancer.Secondary outcome was the OR for down-staging tumor and increasing R0 resection in patients with advanced gastric cancer.Safety analyses were also performed.All calculations and statistical tests were performed using RevMan 5.0 software.tric cancer enrolled in 14 trials were divided into NAC group (n=1054) and control group (n=1217).The patients were followed up for a median time of 54 mo.NAC significantly improved the survival rate [OR=1.27,95% confidence interval (CI):1.04-1.55],tumor stage (OR=1.71,95% CI:1.26-2.33) and R0 resection rate (OR=1.51,95% CI:1.19-1.91) of patients with advanced gastric cancer.No obvious safety concerns were raised in these trials.CONCLUSION:NAC can improve tumor stage and survival rate of patients with advanced gastric cancer with a rather good safety.

Computed tomography-based radiomics for prediction of neoadjuvant chemotherapy outcomes in locally advanced gastric cancer: A pilot study

Objective： The standard treatment for patients with locally advanced gastric cancer has relied on perioperativeradio-chemotherapy or chemotherapy and surgery. The aim of this study was to investigate the wealth of radiomicsfor pre-treatment computed tomography （CT） in the prediction of the pathological response of locally advancedgastric cancer with preoperative chemotherapy.Methods： Thirty consecutive patients with CT-staged Ⅱ/Ⅲ gastric cancer receiving neoadjuvant chemotherapywere enrolled in this study between December 2014 and March 2017. All patients underwent upper abdominal CTduring the unenhanced, late arterial phase （AP） and portal venous phase （PP） before the administration ofneoadjuvant chemotherapy. In total, 19,985 radiomics features were extracted in the AP and PP for each patient.Four methods were adopted during feature selection and eight methods were used in the process of building theclassifier model. Thirty-two combinations of feature selection and classification methods were examined. Receiveroperating characteristic （ROC） curves were used to evaluate the capability of each combination of feature selectionand classification method to predict a non-good response （non-GR） based on tumor regression grade （TRG）.Results： The mean area under the curve （AUC） ranged from 0.194 to 0.621 in the AP, and from 0.455 to 0.722in the PP, according to different combinations of feature selection and the classification methods. There was onlyone cross-combination machine-learning method indicating a relatively higher AUC （〉0.600） in the AP, while 12cross-combination machine-learning methods presented relatively higher AUCs （all 〉0.600） in the PP. The featureselection method adopted by a filter based on linear discriminant analysis ＋ classifier of random forest achieved asignificantly prognostic performance in the PP （AUC, 0.722~0.108; accuracy, 0.793; sensitivity, 0.636; specificity,0.889; Z=2.039; P=0.041）.Conclusions： It is possible to predict non-GR after neoadiuvant chemotherapy in locally advanced gastriccancers based on the radiomics of CT.

CapOX as neoadjuvant chemotherapy for locally advanced operable colon cancer patients: a prospective single-arm phase Ⅱ trial

Objective： The aim of this prospective, single-arm phase II trial was to confirm the safety and efficacy of neoadjuvant chemotherapy（NAC） using oxaliplatin plus capecitabine（Cap OX） for patients with operable locally advanced colon cancer（CC）.Methods： Patients with computed tomography-defined T4 or lymph node-positive CCs were enrolled. After radiological staging, patients were treated with at least 2 cycles of NAC consisting of 130 mg/m2 oxaliplatin on d 1,plus 1,000 mg/m2 capecitabine twice daily for 14 d every 3 weeks, followed by surgery, and then with the rest cycles of adjuvant chemotherapy. Radiological response was evaluated after 2 cycles of NAC. Tumor response, treatment toxicity, and surgical complications were recorded. The pathological response to therapy was evaluated according to the tumor regression grade（TRG） score. The primary endpoint was pathologic tumor response. This trial is registered in Clinical Trials.gov（No： NCT02415829）.Results： Forty-seven patients were enrolled in the study. Forty-two patients completed the planned treatments.The total radiological response rate was 68%（32/47）, including complete and partial response rates of 2%（1/47）and 66%（31/47）, respectively. Stable disease was observed in 32%（15/47） and progressive disease was observed in none. Complete pathologic response, major regression, and at least moderate regression were achieved in 1（2%）, 2（4%）, and 29（62%） patients, respectively. Four patients developed grade 3 treatment toxicities. One patient with wound infection occurred after operation（1/47, 2%）. There was no treatment-related death.Conclusions： Our results suggest that NAC with Cap OX is an effective and safe treatment option for patients with locally advanced CCs.

Primary debulking surgery or neoadjuvant chemotherapy followed by interval debulking surgery for patients with advanced ovarian cancer

Objectives： To compare the survival and perioperafive morbidity between primary debulking surgery （PDS） and neoadjuvant chemotherapy followed by interval debulking surgery （NAC/IDS） in treating patients with advanced epithelial ovarian cancer （EOC）. Methods： We retrospectively reviewed 67 patients with stage IIIC or iV EOC treated at Peking University Cancer Hospital from January 2006 to June 2009. VVherein, 37 and 30 patients underwent PDS and NAC/ IDS, respectively. Results： No difference in overall survival （OS） or progression-free survival （PFS） was observed between NAC/IDS group and PDS group （OS： 41.2 vs. 39.1 months, P=0.23; PFS： 27.1 vs. 24.3 months, P=0.37）. The optimal debulking rate was 60% in the NAC/IDS group, which was significantly higher than that in the PDS group （32.4%） （P=0.024）. The NAC/IDS group had significantly less intraoperative estimated blood loss and transfusion, lower nasogastric intubation rate, and earlier ambulation and recovery of intestinal function than the PDS group （P〈0.05）. Conclusions： NAC/IDS is less invasive than PDS, and offers the advantages regarding optimal cytoreduction rate, intraoperative blood loss, and postoperative recovery, without significantly impairing the survival compared with PDS in treating patients with stage IIIC or IV EOC. Therefore, NAC/IDS may be a valuable treatment alternative for EOC patients.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma:a retrospective comparison of toxicity and prognosis

Background:In the era of intensity?modulated radiotherapy(IMRT),the role of neoadjuvant chemotherapy(NACT)in treating ascending?type nasopharyngeal carcinoma(NPC)is under?evaluated.This study was to compare the efficacy of NACT followed by IMRT(NACT+RT)with the efficacy of concurrent chemoradiotherapy(CCRT)on ascending?type NPC.Methods:Clinical data of 214 patients with ascending?type NPC treated with NACT+RT or CCRT between Decem?ber 2009 and July 2011 were analyzed.Of the 214 patients,98 were treated with NACT followed by IMRT,and 116 were treated with CCRT.The survival rates were assessed using Kaplan–Meier analysis,and the survival curves were compared using a log?rank test.Results:The 4?year overall survival,locoregional failure?free survival,distant failure?free survival,and failure?free sur?vival rates were not significantly different between the two groups(all P>0.05).However,patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT+RT group during radiotherapy,includ?ing leukopenia(30.2%vs.15.3%,P=0.016),neutropenia(25.9%vs.11.2%,P=0.011),and mucositis(57.8%vs.40.8%,P=0.028).After radiotherapy,patients in the CCRT group exhibited significantly higher rates of xerostomia(21.6%vs.Conclusions:The treatment outcomes of the NACT+RT and CCRT groups were similar;however,CCRT led to higher rates of acute and late toxicities.NACT+RT may therefore be a better treatment strategy for ascending?type NPC.

Multi-modal radiomics model to predict treatment response to neoadjuvant chemotherapy for locally advanced rectal cancer

BACKGROUND Neoadjuvant chemotherapy is currently recommended as preoperative treatment for locally advanced rectal cancer(LARC);however,evaluation of treatment response to neoadjuvant chemotherapy is still challenging.AIM To create a multi-modal radiomics model to assess therapeutic response after neoadjuvant chemotherapy for LARC.METHODS This retrospective study consecutively included 118 patients with LARC who underwent both computed tomography(CT)and magnetic resonance imaging(MRI)before neoadjuvant chemotherapy between October 2016 and June 2019.Histopathological findings were used as the reference standard for pathological response.Patients were randomly divided into a training set(n=70)and a validation set(n=48).The performance of different models based on CT and MRI,including apparent diffusion coefficient(ADC),dynamic contrast enhanced T1 images(DCE-T1),high resolution T2-weighted imaging(HR-T2WI),and imaging features,was assessed by using the receiver operating characteristic curve analysis.This was demonstrated as area under the curve(AUC)and accuracy(ACC).Calibration plots with Hosmer-Lemeshow tests were used to investigate the agreement and performance characteristics of the nomogram.RESULTS Eighty out of 118 patients(68%)achieved a pathological response.For an individual radiomics model,HR-T2WI performed better(AUC=0.859,ACC=0.896)than CT(AUC=0.766,ACC=0.792),DCE-T1(AUC=0.812,ACC=0.854),and ADC(AUC=0.828,ACC=0.833)in the validation set.The imaging performance for extramural venous invasion detection was relatively low in both the training(AUC=0.73,ACC=0.714)and validation(AUC=0.578,ACC=0.583)sets.The multi-modal radiomics model reached an AUC of 0.925 and ACC of 0.886 in the training set,and an AUC of 0.93 and ACC of 0.875 in the validation set.For the clinical radiomics nomogram,good agreement was found between the nomogram prediction and actual observation.CONCLUSION A multi-modal nomogram using traditional imaging features and radiomics of preoperative CT and MRI adds accuracy to the prediction of treatment outcome,and thus contributes to the personalized selection of neoadjuvant chemotherapy for LARC.