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.

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.

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 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.

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.

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.

Advances of pathological complete response after neoadjuvant therapy for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor prognosis. Only 15% to 20% of patients present with a primarily resectable tumor at the time of diagnosis. There has been an increasing interest in the use of neoadjuvant chemotherapy alone or combination with radiotherapy in patients with resectable, borderline resectable, and locally advanced pancreatic cancer. Although the benefit of neoadjuvant therapy on resectable patients remains controversial, around one third of borderline resectable and locally advanced patients could be expected to have resectable tumors following neoadjuvant therapy, with comparable survival as those with primary resectable tumors. A pathological complete response (Pcr) in PDAC is an indicator for significantly better survival although it's rather rare. In this review, we present recent progress of Pcr and the controversies in pancreatic cancer after neoadjuvant therapy.

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.

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.

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.

Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

BACKGROUND For locally advanced rectal cancer(LARC),standard therapy[consisting of neoadjuvant chemoradiotherapy(CRT),surgery,and adjuvant chemotherapy(ChT)]achieves excellent local control.Unfortunately,survival is still poor due to distant metastases,which remains the leading cause of death among these patients.In recent years,the concept of total neoadjuvant treatment(TNT)has been developed,whereby all systemic ChT-mainly affecting micrometastases-is applied prior to surgery.AIM To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for failure.METHODS In a retrospective study,we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with TNT.High-risk for failure was defined according to the presence of at least one of the following factors:T4 stage;N2 stage;positive mesorectal fascia;extramural vascular invasion;positive lateral lymph node.TNT consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin,CRT with capecitabine,and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin prior to surgery.The primary endpoint was pathological complete response(pCR).In total,72 patients treated with standard therapy and 89 patients treated with TNT were included in the analysis.RESULTS Compared to standard therapy,TNT showed a higher proportion of pCR(23%vs 7%;P=0.01),a lower neoadjuvant rectal score(median:8.43 vs 14.98;P<0.05),higher T-and N-downstaging(70%and 94%vs 51%and 86%),equivalent R0 resection(95%vs 93%),shorter time to stoma closure(mean:20 vs 33 wk;P<0.05),higher compliance during systemic ChT(completed all cycles 87%vs 76%;P<0.05),lower proportion of acute toxicity grade≥3 during ChT(3%vs 14%,P<0.05),and equivalent acute toxicity and compliance during CRT and in the postoperative period.The pCR rate in patients treated with TNT was significantly higher in patients irradiated with intensity-modulated radiotherapy/volumetricmodulated arc radiotherapy than with 3D conformal radiotherapy(32%vs 9%;P<0.05).CONCLUSION Compared to standard therapy,TNT provides better outcome for LARC patients with high-risk factors for failure,in terms of pCR and neoadjuvant rectal score.

Outcomes of neoadjuvant chemoradiotherapy followed by radical resection for T4 colorectal cancer

BACKGROUND Patients with clinical T4 colorectal cancer(CRC)have a poor prognosis because of compromised surgical margins.Neoadjuvant therapy may be effective in downstaging tumors,thereby rendering possible radical resection with clear margins.AIM To evaluate tumor downsizing and resection with clear margins in T4 CRC patients undergoing neoadjuvant concurrent chemoradiotherapy followed by surgery.METHODS This study retrospectively included 86 eligible patients with clinical T4 CRC who underwent neoadjuvant concurrent chemoradiotherapy followed by radical resection.Neoadjuvant therapy consisted of radiation therapy at a dose of 45-50.4 Gy and chemotherapy agents,either FOLFOX or capecitabine.A circumferential resection margin(CRM)of<1 mm was considered to be a positive margin.We defined pathological complete response(p CR)as the absence of any malignant cells in a specimen,including the primary tumor and lymph nodes.A multivariate logistic regression model was used to identify independent predictive factors for p CR.RESULTS For 86 patients who underwent neoadjuvant chemoradiotherapy and surgery,the rate of p CR was 14%,and the R0 resection rate was 91.9%.Of the 61 patients with rectal cancer,7(11.5%)achieved p CR and 5(8.2%)had positive CRMs.Of the 25 patients with colon cancer,5(20%)achieved p CR and 2(8%)had positive CRMs.We observed that the FOLFOX regimen was an independent predictor of p CR(P=0.046).After a median follow-up of 47 mo,the estimated 5-year overall survival(OS)and disease-free survival(DFS)rates were 70.8%and 61.4%,respectively.Multivariate analysis revealed that a tumor with a negative resection margin was associated with improved DFS(P=0.014)and OS(P=0.001).Patients who achieved p CR exhibited longer DFS(P=0.042)and OS(P=0.003)than those who did not.CONCLUSION Neoadjuvant concurrent chemoradiotherapy engenders favorable p CR and R0 resection rates among patients with T4 CRC.The R0 resection rate and p CR are independent prognostic factors for patients with T4 CRC.

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.

Can cyclin-dependent kinase 4/6 inhibitors convert inoperable breast cancer relapse to operability? A case report

BACKGROUND Pathological complete response(pCR) is rare in hormone receptor-positive(HR+)HER2-negative breast cancer(BC) treated with either endocrine therapy(ET) or chemotherapy. Radical resection of locoregional relapse, although potentially curative in some cases, is challenging when the tumor invades critical structures.The oral cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ET has obtained a significant increase in objective response rates and progression-free survival in patients with advanced BC and is now being evaluated in the neoadjuvant setting. We present a clinical case of a patient with an inoperable locoregional relapse of HR+ HER2-negative BC who experienced p CR after treatment with palbociclib.CASE SUMMARY We report the clinical case of a 60-year-old patient who presented with an inoperable locoregional relapse of HR+, HER2-negative BC 10 years after the diagnosis of the primary tumor. During a routine follow-up visit, breast magnetic resonance imaging and positron emission tomography/computed tomography revealed a 4-cm lesion in the right subclavicular region, infiltrating the chest wall and extending to the subclavian vessels, but without bone or visceral involvement. Treatment was begun with palbociclib plus letrozole, converting the disease to operability over a period of 6 mo. Surgery was performed and a p CR achieved. Of note, during treatment the patient experienced a very uncommon toxicity characterized by burning tongue and glossodynia associated with dysgeusia, paresthesia, dysesthesia, and xerostomia. A reduction in the dose of palbociclib did not provide relief and treatment with the inhibitor was thus discontinued, resolving the tongue symptoms. Laboratory exams were unremarkable. Given that this was a late relapse, the tumor was classified asendocrine-sensitive, a condition associated with high sensitivity to palbociclib.CONCLUSION This case highlights the potential of the cyclin-dependent kinase 4/6 inhibitor plus ET combination to achieve pCR in locoregional relapse of BC, enabling surgical resection of a lesion initially considered inoperable.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer:a single-center,single-arm,prospective Phase II trial(PKUCH-R02)

Background:Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk,locally advanced rectal cancer.However,the benefit of more intensive total neoadjuvant treatment(TNT)is unknown.This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer.Methods:This was a single-center,single-arm,prospective Phase II trial in Peking University Cancer Hospital(Beijing,China).Patients received three cycles of induction oxaliplatin and capecitabine(CapeOX)followed by chemoradiotherapy and two cycles of consolidation CapeOX.The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate,completion of TNT,and pathological downstaging rate.Results:Between August 2017 and August 2018,68 rectal cancer patients with at least one high risk factor(cT3c/3d/T4a/T4b,cN2,mesorectal fascia involvement,or extramural venous invasion involvement)were enrolled.The overall compliance of receiving the entire treatment was 88.2%(60/68).All 68 patients received induction chemotherapy,65 received chemoradiotherapy,and 61 received consolidation chemotherapy.The Grade 3–4 adverse event rate was 30.8%(21/68).Nine patients achieved clinical complete response and then watch and wait.Five patients(7.4%)developed distant metastasis during TNT and received palliative chemotherapy.Fifty patients underwent surgical resection.The complete response rate was 27.9%.After a median follow-up of 49.2 months,the overall 3-year disease-free survival rate was 69.7%.Conclusions:For patients with high-risk rectal cancer,this TNT regimen can achieve favorable survival and complete response rates but with high toxicity.However,it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

预测局部进展期直肠癌病理完全缓解和肿瘤降期的nomogram模型:基于一项随机对照研究数据的分析

背景:氟尿嘧啶为基础的术前化放疗被认为是局部进展期直肠癌(LARC)的标准治疗。当前一些预测LARC患者新辅助治疗后临床病理缓解(pCR)的nomogram模型仅仅是针对的是这一标准方案。本研究基于一项随机对照临床研究数据,利用新辅助治疗前临床病理参数,旨在建立一个用以预测不同方案新辅助治疗后pCR和肿瘤降期(ypT0-2N0M0)的nomogram模型。方法:从一项前瞻性随机对照研究(NCT01211210)中提取2011年1月至2015年2月间入组的309例LARC病例。收集所有新辅助治疗前临床参数建立预测pCR和肿瘤降期的nomogram模型。采用bootstrap法对模型进行内部验证。采用一致性指数(C-index)和校准曲线评估模型的预测价值。结果:309例患者中,53例(17.2%)获得pCR,132例(42.7%)ypT0-2N0M0患者判定为肿瘤降期。基于逻辑回归分析和临床考量,肿瘤大小(P¼0.005)、环周累及范围(P¼0.036)、肿瘤距肛缘距离(P¼0.019)和新辅助治疗方案(P<0.001)是pCR的独立预测因素;肿瘤大小(P¼0.015)、环周累及范围(P¼0.001)、肿瘤距肛缘距离(P¼0.032)、临床T分期(P¼0.012)和新辅助治疗方案(P¼0.001)是肿瘤降期的独立预测因素。基于上述因素建立的pCR预测模型和肿瘤降期预测模型,其预测结果与实际临床观察结果的C-index分别为0.802(90%CI:0.736-0.867)和0.730(95%CI:0.672-0.784)。内部验证的校正曲线也显示出了良好的预测价值。结论:本研究建立的nomogram模型能为不同新辅助治疗方案的直肠癌患者提供个体化预测。该模型有助于临床医生的治疗选择,但需要进一步外部验证。