Complete pathological response in locally advanced non-small-cell lung cancer patient: A case report

BACKGROUND Chemotherapy and radiotherapy followed by durvalumab is currently the standard treatment for locally advanced node-positive non-small-cell lung cancer(NSCLC).We describe the case of a patient with locally advanced node-positive NSCLC(LA-NSCLC)treated in a phase II prospective protocol with chemotherapy,accelerated hypofractionated radiotherapy(AHRT)and surgery in the preimmunotherapy era.CASE SUMMARY A 69-year-old male,ex-smoker(20 PY),with a Karnofsky performance status of 90,was diagnosed with locally advanced squamous cell lung carcinoma.He was staged by total body computed tomography(CT)scanning,and integrated 18Ffluorodeoxyglucose positron emission tomography/CT scan[cT4 cN3 cM0,stage IIIC according to TNM(tumor-node-metastasis)8th edition]and received AHRT between chemotherapy cycles,in accordance with the study protocol(EudractCT registration 2008-006525-14).At the end of the study the patient underwent surgery,which was not part of the protocol,and showed a complete pathological response.CONCLUSION This case report confirms that AHRT can be used successfully to treat primary LA-NSCLC with bilateral mediastinal lymph node involvement.Our case is of particular interest because of the pathological response after AHRT and the lack of surgical complications.We hypothesize that this radiotherapeutic approach,with its proven efficacy,could be delivered as a short course reducing treatment costs,increasing patient compliance and reducing toxicity.We are currently investigating the possibility of combining hypofractionation,chemotherapy and immunotherapy for patients with LA-NSCLC.

Pathological response to neoadjuvant therapy with chemotherapy vs chemoradiotherapy in stage III NSCLC-contribution of IASLC recommendations

BACKGROUND Neoadjuvant treatment(NT)with chemotherapy(Ch)is a standard option for resectable stage III(N2)NSCLC.Several studies have suggested benefits with the addition of radiotherapy(RT)to NT Ch.The International Association for the Study of Lung Cancer(IASLC)published recommendations for the pathological response(PHR)of NSCLC resection specimens after NT.AIM To contribute to the IASLC recommendations showing our results of PHR to NT Ch vs NT chemoradiotherapy(ChRT).METHODS We analyzed 67 consecutive patients with resectable stage III NSCLC with positive mediastinal nodes treated with surgery after NT Ch or NT ChRT between 2013 and 2020.After NT,all patients were evaluated for radiological response(RR)according to Response Evaluation Criteria in Solid Tumours criteria and evaluated for surgery by a specialized group of thoracic surgeons.All histological samples were examined by the same two pathologists.PHR was evaluated by the percentage of viable cells in the tumor and the resected lymph nodes.RESULTS Forty patients underwent NT ChRT and 27 NT Ch.Fifty-six(83.6%)patients underwent surgery(35 ChRT and 21 Ch).The median time from ChRT to surgery was 6 wk(3-19)and 8 wk(3-21)for Ch patients.We observed significant differences in RR,with disease progression in 2.5%and 14.8%of patients with ChRT and Ch,respectively,and partial response in 62.5%ChRT vs 29.6%Ch(P=0.025).In PHR we observed≤10%viable cells in the tumor in 19(54.4%)and 2 cases(9.5%),and in the resected lymph nodes(RLN)30(85.7%)and 7(33.3%)in ChRT and Ch,respectively(P=0.001).Downstaging was greater in the ChRT compared to the Ch group(80%vs 33.3%;P=0.002).In the univariate analysis,NT ChRT had a significant impact on partial RR[odds ratio(OR)12.5;95%confidence interval(CI):1.21-128.61;P=0.034],a decreased risk of persistence of cancer cells in the tumor and RLN and an 87.5%increased probability for achieving downstaging(OR 8;95%CI:2.34-27.32;P=0.001).CONCLUSION We found significant benefits in RR and PHR by adding RT to Ch as NT.A longer follow-up is necessary to assess the impact on clinical outcomes.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

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.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol.Immunotherapy has achieved breakthrough progress.CASE SUMMARY We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0.Detection of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR.Surprisingly,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after surgery.CONCLUSION PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

Nomogram for predicting axillary lymph node pathological response in node-positive breast cancer patients after neoadjuvant chemotherapy

Background:Pathological complete response(pCR)of axillary lymph nodes(ALNs)is frequently achieved in patients with clinically node-positive breast cancer after neoadjuvant chemotherapy(NAC),and ALN status is an important prognostic factor for breast cancer patients.This study aims to develop a new predictive clinical model to assess the ALN pCR rate after NAC.Methods:This was a retrospective series of 467 patients who had biopsy-proven positive ALNs at diagnosis and underwent ALN dissection from 2007 to 2014 at the National Cancer Center/Cancer Hospital of the Chinese Academy of Medical Sciences.We analyzed the clinicopathologic features of the patients and developed a nomogram to predict the probability of ALN pCR.A multivariable logistic regression stepwise model was used to construct a nomogram to predict ALN pCR in node-positive patients.The adjusted area under the receiver operating characteristic curve(AUC)was calculated to quantify the ability to rank patients by risk.Internal validation was performed using the 50/50 hold-out validation method.The nomogram was externally validated with prospective cohorts of 167 patients from 2016 to 2018 at the Cancer Hospital of the Chinese Academy of Medical Sciences and 114 patients from 2018 to 2020 at Beijing Tiantan Hospital.Results:In this retrospective study,115(24.6%)patients achieved ALN pCR after NAC.Multivariate analysis showed that clinical tumor stage(Odds ratio[OR]:0.321,95%confidence interval[CI]:0.121-0.856;P=0.023);primary tumor response(OR:0.189;95%CI:0.123-0.292;P<0.001),and estrogen receptor status(OR:0.530,95%CI:0.304-0.925;P=0.025)were independent predictors of ALN pCR.The nomogram was constructed based on the result of multivariate analysis.In the internal validation of performance of nomogram,the AUCs for the training and test sets were 0.719 and 0.753,respectively.The nomogram was validated in external cohorts with AUCs of 0.720,which demonstrated good discriminatory power in these data sets.Conclusion:We developed a nomogram to predict the likelihood of axillary pCR in node-positive breast cancer patients after NAC.The predictive model performed well in multicenter prospective external validation.This practical tool could provide information to surgeons regarding whether to perform additional ALN dissection after NAC.Trial registration:ChiCTR.org.cn,ChiCTR1800014968.

Impact of pathological response after preoperative transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma:a multicenter propensity score matching analysis

Background:To study the influence of pathological responses(PR)after transcatheter arterial chemoembolization(TACE)on incidences of microvascular invasion(MVI)and early recurrence in hepatocellular carcinoma(HCC)patients.Methods:Between 2013 to 2015,consecutive HCC patients who underwent liver resection with“curative”intent at three hospitals were enrolled in this study.Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI,early recurrence rates and patterns of recurrence before and after propensity score matching(PSM).Results:Of 1,970 patients,737 patients who received preoperative TACE were divided into three groups according to the areas of PR:≥90%(n=226),60-90%(n=447),and<60%(n=64).PR≥90%was an independent protective factor of incidences of MVI[odds ratio(OR),0.144;95%confidence interval(CI),0.082-0.245,P<0.001)and early recurrence(HR,0.742;95%CI,0.561-0.963,P=0.032);while PR<60%was an independent risk factor of incidences of MVI(OR,6.076;95%CI,3.004-11.728,P<0.001)and early recurrence(HR,1.428;95%CI,1.095-1.929;P=0.009).Furthermore,patients with PR<60%were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.Conclusions:This study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence.Patients with PR<60%were at significantly higher risks of having more MVI,early and multiple tumor recurrences.

Nomogram for predicting pathological complete response to neoadjuvant chemotherapy in patients with advanced gastric cancer

BACKGROUND Survival benefit of neoadjuvant chemotherapy(NAC)for advanced gastric cancer(AGC)is a debatable issue.Studies have shown that the survival benefit of NAC is dependent on the pathological response to chemotherapy drugs.For those who achieve pathological complete response(pCR),NAC significantly prolonged prolapsed-free survival and overall survival.For those with poor response,NAC yielded no survival benefit,only toxicity and increased risk for tumor progression during chemotherapy,which may hinder surgical resection.Thus,predicting pCR to NAC is of great clinical significance and can help achieve individualized treatment in AGC patients.AIM To establish a nomogram for predicting pCR to NAC for AGC patients.METHODS Two-hundred and eight patients diagnosed with AGC who received NAC followed by resection surgery from March 2012 to July 2019 were enrolled in this study.Their clinical data were retrospectively analyzed by logistic regression analysis to determine the possible predictors for pCR.Based on these predictors,a nomogram model was developed and internally validated using the bootstrap method.RESULTS pCR was confirmed in 27 patients(27/208,13.0%).Multivariate logistic regression analysis showed that higher carcinoembryonic antigen level,lymphocyte ratio,lower monocyte count and tumor differentiation grade were associated with higher pCR.Concordance statistic of the established nomogram was 0.767.CONCLUSION A nomogram predicting pCR to NAC was established.Since this nomogram exhibited satisfactory predictive power despite utilizing easily available pretreatment parameters,it can be inferred that this nomogram is practical for the development of personalized treatment strategy for AGC patients.

Unfavorable Pathological Complete Response Rate of Neoadjuvant Chemotherapy Epirubicin plus Taxanes for Locally Advanced Triple-negative Breast Cancer

Anthracycline-Taxane chemotherapy is widely used in neoadjuvant treatment for breast cancers. However, there is limited data reported in patients with triple negative breast cancer （TNBC）. Here, we evaluated the pathologic responses and survival of neoadjuvant epirubicin and taxanes chemotherapy in patients with locally advanced TNBC to provide some useful information for clinical practice. A total of 43 patients with locally advanced TNBC were enrolled in this study. Patients were administered with epirubicin 75 mg/m^2 plus paclitaxel 175 mg/m^2 or docetaxel 75 mg/m^2 every 3 weeks for at least 2 cycles. The primary endpoint was pathologic complete response （pCR）, which was defined as no residual invasive cancer, or only carcinoma in situ in both the excised breast and axillary lymph node, while relapse-free survival （RFS） and overall survival （OS） were secondary endpoints. Thirty-nine （90.7%） patients were at clinical stages II B-IIIC. Thirty-seven （86%） completed 4-6 cycles of preop- erative chemotherapy, and objective response rate （ORR） was 81.4% （35/43）. Forty-two patients un- derwent radical surgery subsequently. The pCR rate was 14.3% （6/42）. The most common adverse events in neoadjuvant chemotherapy were nausea/vomiting （88.4%, 38/43） and neutropenia （88.4%）. After a median follow-up period of 34.0 months, 3-year RFS and OS rate was 53.6% and 80.1%, respectively. All events of recurrence and death occurred in non-pCR patients, in whom the 3-year RFS and OS rates were 44.3% and 76.6%, respectively. This study suggest that neoadjuvant chemotherapy with epirubicin plus taxanes has a relatively low pCR rate and high early recurrence risk in locally ad- vanced TNBC, which indicates the necessity for more efficacious treatment. Further study is needed to validate these results.

Combining prognostic value of serum carbohydrate antigen 19-9 and tumor size reduction ratio in pancreatic ductal adenocarcinoma

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a common cancer with increasing morbidity and mortality due to changes of social environment.AIM To evaluate the significance of serum carbohydrate antigen 19-9(CA19-9)and tumor size changes pre-and post-neoadjuvant therapy(NAT).METHODS This retrospective study was conducted at the Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,Chongqing University Cancer Hospital.This study specifically assessed CA19-9 levels and tumor size before and after NAT.RESULTS A total of 156 patients who completed NAT and subsequently underwent tumor resection were included in this study.The average age was 65.4±10.6 years and 72(46.2%)patients were female.Before survival analysis,we defined the post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level as the CA19-9 ratio(CR).The patients were divided into three groups:CR<0.5,CR>0.5 and<1 and CR>1.With regard to tumor size measured by both computed tomography and magnetic resonance imaging,we defined the post-NAT tumor size/pre-NAT tumor size as the tumor size ratio(TR).The patients were then divided into three groups:TR<0.5,TR>0.5 and<1 and TR>1.Based on these groups divided according to CR and TR,we performed both overall survival(OS)and disease-free survival(DFS)analyses.Log-rank tests showed that both OS and DFS were significantly different among the groups according to CR and TR(P<0.05).CR and TR after NAT were associated with increased odds of achieving a complete or near-complete pathologic response.Moreover,CR(hazard ratio:1.721,95%CI:1.373-3.762;P=0.006),and TR(hazard ratio:1.435,95%CI:1.275-4.363;P=0.014)were identified as independent factors associated with OS.CONCLUSION This study demonstrated that post-NAT serum CA19-9 level/pre-NAT serum CA19-9 level and post-NAT tumor size/pre-NAT tumor size were independent factors associated with OS in patients with PDAC who received NAT and subsequent surgical resection.

Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma:a single center experience

Objective:To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy(RT)or concurrent chemoradiotherapy(CCRT).Methods:This study recruited 64 patients.The patients had resectable cancer of the lower and the middle rectum(T3/T4 and/or N+)without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal excision(TME)between January 2006 and December 2011.The patients were classified into non-response(NR),partial response(PR),and pathologic complete response(p CR)based on the Dworak tumor regression grading system.Results:The median age of patients was 57 years(ranging from 22 to 85).A total of 24 patients were treated with neoadjuvant CCRT,whereas 40 patients were treated with RT alone.Abdominoperineal resection(APR)was performed on 29 patients(45%).Anterior resection with TME was performed on 34 patients(53%).One patient had local resection.Histologically,12(19%),24(73%),and 28(44%)patients exhibited p CR,PR,and NR,respectively.Univariate analysis revealed that the predictors of tumor regression were as follows:the absence of lymph node involvement from initial imaging(c N0)(P=0.021);normal initial carcinoembryonic antigen(CEA)level(P=0.01);hemoglobin level≥12 g/dl(P=0.009);CCRT(P=0.021);and tumor downstaging in imaging(P=0.001).Multivariate analysis showed that the main predictors of p CR were CT combined with neoadjuvant RT,c N0stage,and tumor regression on imaging.Conclusions:Identifying the predictors of p CR following neoadjuvant therapy aids the selection of responsive patients for nonaggressive surgical treatment and possible surveillance.

Predictors of pathologic complete response in patients with residual flat mucosal lesions after neoadjuvant chemoradiotherapy for locally advanced rectal cancer

Objective:The accurate prediction of tumor response to neoadjuvant chemoradiotherapy(nCRT)remains challenging.Few studies have investigated pathologic complete response(ypCR)prediction in patients with residual flat mucosal lesions after treatment.This study aimed to identify variables for predicting ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer(LARC).Methods:Data of patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected from the LARC database at Peking University Cancer Hospital.Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed,and a nomogram was constructed by incorporating the significant predictors.Results:Of the 246 patients with residual flat mucosal lesions included in the final analysis,56(22.8%)had ypCR.Univariate and multivariate analyses showed that pretreatment cT stage(pre-cT)≤T2(P=0.016),magnetic resonance tumor regression grade(MR-TRG)1-3(P=0.001)and residual mucosal lesion depth=0 mm(P<0.001)were associated with a higher rate of ypCR.A nomogram was developed with a concordance index(C-index)of0.759 and the calibration curve showed that the nomogram model had good predictive consistency.The follow-up time ranged from 3.0 to 113.3 months,with a median follow-up time of 63.77 months.The multivariate Cox regression model showed that the four variables in the nomogram model were not risk factors for disease-free survival(DFS)or overall survival(OS).Conclusions:Completely flat mucosa,early cT stage and good MR-TRG were predictive factors for ypCR instead of DFS or OS in patients with LARC with residual flat mucosal lesions after nCRT.Endoscopic mucosal re-evaluation before surgery is important,as it may contribute to decision-making and facilitate nonoperative management or organ preservation.

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.

Successful multidisciplinary therapy for a patient with liver metastasis from ascending colon adenocarcinoma:A case report and review of literature

BACKGROUND Liver metastasis is the most common form of distant metastasis in colorectal cancer,and the only possible curative treatment for patients with colorectal liver metastases(CRLM)is hepatectomy.However,approximately 25%of patients with CRLM have indications for liver resection at the initial diagnosis.Strategies aimed at downstaging large or multifocal tumors to enable curative resection are appealing.CASE SUMMARY A 42-year-old man was diagnosed with ascending colon cancer and liver metastases.Due to the huge lesion size and compression of the right portal vein,the liver metastases were initially diagnosed as unresectable lesions.The patient was treated with preoperative transcatheter arterial chemoembolization(TACE)consisting of 5-fluorouracil/Leucovorin/oxaliplatin/Endostar®.After four courses,radical right-sided colectomy and ileum transverse colon anastomosis were performed.Postoperatively,the pathological analysis revealed moderately differentiated adenocarcinoma with necrosis and negative margins.Thereafter,S7/S8 partial hepatectomy was performed after two courses of neoadjuvant chemotherapy.Pathological examination of the resected specimen revealed a pathologically complete response(pCR).Intrahepatic recurrence was detected more than two months after the operation,and the patient was then treated with TACE consisting of irinotecan/Leucovorin/fluorouracil therapy plus Endostar®.Subsequently,the patient was treated with aγ-knife to enhance local control.Notably,a pCR was reached,and the patient's overall survival time was>9 years.CONCLUSION Multidisciplinary treatment can promote the conversion of initially unresectable colorectal liver metastasis and facilitate complete pathological remission of liver lesions.

Conversion immunotherapy for deficient mismatch repair locally unresectable colon cancer:A case report

BACKGROUND Owing to the special features of biologics,deficient mismatch repair(dMMR)in patients with colon cancer has achieved little treatment efficacy from chemoradiotherapy.Immunotherapy has shown promising results for the treatment of colon cancer.The high response rate observed suggests a great option for patients presenting with unresectable tumors,as it allows for better oncological resection.Here,we aimed to highlight the significant effects of immunotherapy on dMMR in colon cancer.CASE SUMMARY A 54-year-old man diagnosed with locally unresectable dMMR colon cancer received preoperative immunotherapy(three cycles of pembrolizumab)and achieved a pathological complete response after surgery.CONCLUSION Immunotherapy can be used as a conversion treatment for locally unresectable colon cancer with dMMR.

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 treatment in non-small cell lung cancer:New perspectives with the incorporation of immunotherapy

The aim of neoadjuvant treatment in non-small cell lung cancer(NSCLC)is to eliminate micrometastatic disease to facilitate surgical resection.Neoadjuvant chemotherapy(ChT)in localised NSCLC has numerous advantages over other therapeutic modalities and is considered standard treatment in resectable disease.Treatment with immune checkpoint inhibitors(ICI)improves long-term survival in advanced disease and has a better toxicity profile than conventional therapies.These immunotherapy agents(anti-PD1/PD-L1),administered with or without ChT,are currently being evaluated in the preoperative setting,with initial results showing better pathological response rates and more long-term benefits.Importantly,these drugs do not appear to increase the rate of severe adverse effects and/or postoperative complications.However,several questions still need to be resolved,including the identification of predictive biomarkers;comparative studies of immunotherapy alone vs combined treatment with ChT and/or radiotherapy;the optimal duration of treatment;the timing of surgery;the need for adjuvant treatment;appropriate radiologic evaluation and mediastinal staging;and the correlation between pathological response and survival outcomes.Here we review the current evidence for immunotherapy from a multidisciplinary perspective and discuss current and future controversies.

Impact of interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients

BACKGROUND Epidemiologically,in China,locally advanced rectal cancer is a more common form of rectal cancer.Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of locally invasive tumors and improve disease-free survival(DFS)and pathologic response after surgery.At present,this modality has become the standard protocol for the treatment of locally advanced rectal cancer in many centers,but the optimal time for surgery after neoadjuvant therapy is still controversial.AIM To investigate the impact of time interval between neoadjuvant therapy and surgery on DFS and pathologic response in patients with locally advanced rectal cancer.METHODS A total of 231 patients who were classified as having clinical stage II or III advanced rectal cancer and underwent neoadjuvant chemoradiation followed by surgery at the National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College from November 2014 to August 2017 were involved in this retrospective cohort study.The patients were divided into two groups based on the different time intervals between neoadjuvant therapy and surgery:139(60.2%)patients were in group A(≤9 wk),and 92(39.2%)patients were in group B(>9 wk).DFS and pathologic response were analyzed as the primary endpoints.The secondary endpoints were postoperative complications and sphincter preservation.RESULTS For the 231 patients included,surgery was performed at≤9 wk in 139(60.2%)patients and at>9 wk in 92(39.8%).The patients’clinical characteristics,surgical results,and tumor outcomes were analyzed through univariate analysis combined with multivariate regression analysis.The overall pathologic complete response(pCR)rate was 27.2%(n=25)in the longer time interval group(>9 wk)and 10.8%(n=15)in the shorter time interval group(≤9 wk,P=0.001).The postoperative complications did not differ between the groups(group A,5%vs group B,5.4%;P=0.894).Surgical procedures for sphincter preservation were performed in 113(48.9%)patients,which were not significantly different between the groups(group A,52.5%vs group B,43.5%;P=0.179).The pCR rate was an independent factor affected by time interval(P=0.009;odds ratio[OR]=2.668;95%CI:1.276-5.578).Kaplan-Meier analysis and Cox regression analysis showed that the longer time interval(>9 wk)was a significant independent prognostic factor for DFS(P=0.032;OR=2.295;95%CI:1.074-4.905),but the time interval was not an independent prognostic factor for overall survival(P>0.05).CONCLUSION A longer time interval to surgery after neoadjuvant therapy may improve the pCR rate and DFS but has little impact on postoperative complications and sphincter preservation.

Application of neoadjuvant chemotherapy combined with anlotinib in occult breast cancer:A case report and review of literature

BACKGROUND Occult breast cancer(OBC)is a special type of breast cancer presenting as axillary lymph node metastasis with undetectable primary lesions in the breast.Due to its low incidence and unique clinical manifestations,there is a lack of consensus on the diagnosis and treatment of OBC.We report a case of OBC treated with neoadjuvant chemotherapy combined with anlotinib.The treatment was well tolerated,and the patient achieved a pathologic complete response.CASE SUMMARY A 53-year-old woman presented with a lump in her right axillary area with no primary lesions in the breast.Pathological biopsy confirmed right axillary metastatic carcinoma.Immunohistochemical staining results were positive for progesterone receptor,cytokeratin 7,specific breast markers GATA3 and gross cystic disease fluid protein-15.Tumor cells were negative for estrogen receptor,human epidermal growth factor receptor-2,cytokeratin 5/6,cytokeratin 20,and villin.The patient was diagnosed with OBC,and she underwent neoadjuvant chemotherapy combined with anlotinib.Mastectomy plus axillary lymph node dissection was performed.The patient achieved pathologic complete response with no residual invasive tumor cells in the breast or axillary lymph nodes.Postoperatively,she received adjuvant radiotherapy and endocrine therapy.CONCLUSION Neoadjuvant chemotherapy and anlotinib had good efficacy and safety in the treatment of OBC and may be a new therapeutic option.

Neoadjuvant Therapy for Advanced Rectal Carcinoma in China:Whether Radiochemotherapy Is Superior to Radiotherapy?

Objective： To verify whether the 30 Gy preoperative radiotherapy regimen is effective to advanced rectal cancer, and whether the preoperative chemoradiation offers an advantage in sphincter preservation and tumor control compared with irradiation alone. Methods： A total of 141 patients administered neoadjuvant treatment with resectable lower rectal carcinoma from 2002 to 2006 were collected retrospectively. The patients were divided into two groups： preoperative radiotherapy alone （30Gy by 10 fractions） （PRT group） and preoperative chemoradiotherapy （PCRT group）. All patients underwent radical surgery after neoadjuvant treatment. Results： The overall sphincter-preservation rate was 68.8% （97/141）, with no significant difference between the two groups. The overall downstaging rate was 48.2% （68/141）, including 4 patients completely response （2.8%）. The T and N downstaging rate were 30.5% （43/141） and 53.8% （57/106） respectively, showing no statistically difference between the two groups. The 2-year overall survival rate was 93.6%; no survival benefit were observed in PCRT group. The 2-year cumulative local recurrence rates were similar as well （4.2% vs 6.7%, P=0.63）. Two patients with severe marrow suppression higher than grade 3 and 1 patient with severe perineum ulcer was observed in PCRT group, which did not occur in PRT group. Conclusion： The preoperative adjuvant treatment of 30Gy radiotherapy alone may be an optional treatment for Chinese lower rectal carcinoma. Preoperative chemoradiotherapy does not show actual superiority compared with radiotherapy alone.