Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Prognosis of radiotherapy for esophageal cancer in elderly patients exceeding seventy-five years old

BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy

AIM:To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma(SCC) treated with three dimensional conformal radiotherapy(3D-CRT).METHODS:Between January 2005 and December 2006,153 patients(120 males,33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis.Median age was 60 years(range:37-84 years).The proportion of tumor location was as follows:upper thorax(including the cervical region),73(48%);middle thorax,73(48%);lower thorax,7(5%),respectively.The median radiation dose was 64 Gy(range:50-74 Gy).Fifty four cases(35%) received cisplatin-based concurrent chemotherapy.Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis.RESULTS:The five-year overall survival rate was 26.3%,with a median follow-up of 49 mo(range:3-66 mo) for patients who were still alive.On univariate analysis,lesion location,lesion length by barium esophagogram,computed tomography imaging characteristics including Y diameter(anterior-posterior,AP,extent of tumor),gross tumor volume of primary lesion(GTV-E),volume of positive lymph nodes(GTV-LN),and the total target volume(GTV-T = GTV-E + GTVLN) were prognostic for overall survival.By multivariate analysis,only the Y diameter [hazard ratio(HR) 2.219,95%CI 1.141-4.316,P = 0.019] and the GTV-T(HR 1.372,95%CI 1.044-1.803,P = 0.023) were independent prognostic factors for survival.CONCLUSION:The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising.The best predictors for survival were GTV-T and Y diameter.

Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer

AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC).

Concurrent chemoradiotherapy combined with enteral nutrition support:a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant istulae

Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term survival.Methods: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at Sun Yat?sen University Cancer Center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of CCRT.Results: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during treatment.Conclusions: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be cured, especially those who experience complete response and have an increase in NRS score. Careful observation and nutrition support are required for patients with advanced T?category ESCC who undergo CCRT.

Computed tomography overestimation of esophageal tumor length: Implications for radiotherapy planning

AIM:To assess the relationship between preoperative computed tomography(CT)and postoperative pathological measurements of esophageal tumor length and the prognostic significance of CT tumor length data.METHODS:A retrospective study was carried out in 56 patients who underwent curative esophagogastrectomy.Tumor lengths were measured on the immediate preoperative CT and on the post-operative resection specimens.Inter-and intra-observer variations in CT measurements were assessed.Survival data were collected.RESULTS:There was a weak correlation between CT and pathological tumor length(r=0.30,P=0.025).CT lengths were longer than pathological lengths in 68%(38/56)of patients with a mean difference of 1.67 cm(95%CI:1.18-2.97).The mean difference in measurements by two radiologists was 0.39 cm(95% CI:-0.59-1.44).The mean difference between repeat CT measured tumor length(intra-observer variation) were 0.04 cm(95%CI:-0.59-0.66)and 0.47 cm (95%CI:-0.53-1.47).When stratified,patients not receiving neoadjuvant chemotherapy showed a strong correlation between CT and pathological tumor length(r =0.69,P=0.0014,n=37)than patients that did(r= 0.13,P=0.43,n=19).Median survival with CT tumor length>5.6 cm was poorer than with smaller tumors,but the difference was not statistically significant.CONCLUSION:Esophageal tumor length assessed using CT does not reflect pathological tumor extent and should not be the only modality used for management decisions,particularly for planning radiotherapy.

Correlation of plasma miR-21 and miR-93 with radiotherapy and chemotherapy efficacy and prognosis in patients with esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the main causes of human death.It is usually already in middle or advanced stage when diagnosed due to its hidden symptoms in early stage.Therefore,patients have already lost the best surgical timing when diagnosed.Radiotherapy and chemotherapy are standard treatment methods for ESCC clinically,but the efficacy and prognosis of patients from them are still unsatisfactory.Therefore,it is of great clinical significance to seek for biomarkers that can predict the radiotherapy and chemotherapy response and prognosis of ESCC patients.AIM To explore the clinical value of plasma miR-21 and miR-93 in ESCC.METHODS A total of 128 ESCC patients admitted to the First Affiliated Hospital of Zhenzhou University were enrolled as a study group and treated with concurrent radiotherapy and chemotherapy,and other 45 healthy people during the same period were enrolled as a control group.The expression of plasma miR-21 and miR-93 was determined using quantitative real-time polymerase chain reaction,and the correlation of expression of plasma miR-21 and miR-93 with clinical pathological parameters about the patients was analyzed.The receiver operating characteristic(ROC)curve was adopted to assess the diagnostic value of plasma miR-21 and miR-93 for clinical pathological features of ESCC patients,the Logistic regression analysis adopted to analyze the risk factors for radiotherapy and chemotherapy efficacy in ESCC patients,and the Cox regression analysis to identify the prognostic factors for ESCC patients.RESULTS The study group showed significantly higher relative expression of plasma miR-21 and miR-93 than the control group(P<0.01).The area under the ROC curve(AUC)of plasma miR-21 for diagnosing T stage,N stage,M stage,and pathological differentiation of ESCC was 0.819,0.758,0.824,and 0.725,respectively,and that of plasma miR-93 for diagnosing T stage,N stage,and M stage of ESCC was 0.827,0.815,and 0.814,respectively.The AUC of combined plasma miR-21 and miR-93 for predicting radiotherapy and chemotherapy efficacy before radiotherapy and chemotherapy was 0.894,and the AUCs of them for predicting the 3-year overall survival(OS)were 0.861 and 0.807,respectively.T stage(P<0.05),M stage(P<0.05),miR-21(P<0.01),and miR-93(P<0.05)were independent risk factors for radiotherapy and chemotherapy efficacy,and T stage(P<0.01),N stage(P<0.05),M stage(P<0.01),miR-21(P<0.01),and miR-93(P<0.01)were independent prognostic factors for ESCC patients.CONCLUSION MiR-21 and miR-93 can be adopted as effective biomarkers for predicting radiotherapy and chemotherapy efficacy in ESCC and the 3-year OS of ESCC patients.

Technological advances in radiotherapy for esophageal cancer

Radiotherapy with concurrent chemotherapy and surgery represent the main treatment modalities in esophageal cancer.The goal of modern radiotherapy approaches,based on recent technological advances,is to minimize post-treatment complications by improving the gross tumor volume definition (positron emission tomography-based planning),reducing interfraction motion (image-guided radiotherapy) and intrafraction motion (respiratory-gated radiotherapy),and by better dose delivery to the precisely defined planning target volume (intensity-modulated radiotherapy and proton therapy).Reduction of radiotherapy-related toxicity is fundamental to the improvement of clinical results in esophageal cancer,although the dose escalation concept is controversial.

Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma

AIM:To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis.METHODS:PubMed and manual searches were done to identify all published randomized controlled trials(RCTs) that compared neoadjuvant chemoradiotherapy plus surgery(CRTS) with surgery alone(S) for esophageal cancer.According to the test of heterogeneity,a fi xed-effect model or a random effect model was used and the odds ratio(OR) was the principal measure of effects.RESULTS:Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C(Cochrane Reviewers' Handbook 4.2.2).OR(95% CI,P value),expressed as CRTS vs S(values>1 favor CRTS arm),was 1.19(0.94-1.48,P=0.28) for 1-year survival,1.33(1.07-1.65,P=0.69) for 2-year survival,1.76(1.42-2.19,P=0.11) for 3-year survival,1.41(1.06-1.87,P=0.11) for 4-year survival,1.64(1.28-2.12,P=0.40) for 5-year survival,0.82(0.39-1.73,P<0.0001) for rate of resection,1.53(1.33-2.84,P=0.007) for rate of complete resection,1.78(1.14-2.78,P=0.79) for operative mortality,1.12(0.89-2.48,P=0.503) for all treatment mortality,1.33(0.94-1.88,P=0.04) for the rate of adverse treatment,1.38(1.23-1.63,P=0.0002) for local-regional cancer recurrence,1.28(0.85-1.58,P=0.60) for distant cancer recurrence,and 1.27(0.86-1.65,P=0.19) for all cancer recurrence.A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients.The 5-year survival benefi t was most pronounced when chemotherapy and radiotherapy were given concurrently(OR:1.45,95% CI:1.26-1.79,P=0.015) instead of sequentially(OR:0.85,95% CI:0.64-1.35,P=0.26).CONCLUSION:Compared with surgery alone,neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence.Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.

Radiotherapy of double primary esophageal carcinoma

INTRODUCTIONDouble primary esophageal carcinoma is defined ashaving two loci of squamous cell cancersimultaneously or consecutively developing indifferent sites of esophagus.This rare diseaseappears mostly in the literature as case reports,reports about its treatment are even moreinfrequent.Here we present our experiences

Predictors of post-treatment stenosis in cervical esophageal cancer undergoing high-dose radiotherapy

AIM To evaluate toxicity and treatment outcome of highdose radiotherapy(RT) for cervical esophageal cancer(CEC).METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage Ⅰ to Ⅲ cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local(occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed.RESULTS Grade 1, 2, and 3 esophagitis occurred in 19(30.6%), 39(62.9%), and 4 patients(6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients(25.8%) developed post-RT stenosis, of which 7 cases(43.8%) were malignant. Four patients(6.5%) developed tracheoesophageal fistula(TEF), of which 3(75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4(P = 0.001), complete circumference involvement(P < 0.0001), stenosis at diagnosis(P = 0.024), and endoscopic complete response(P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis(P = 0.003). A higher dose(≥ 60 Gy) was not associated with occurrence of postRT stenosis or TEF. With a median follow-up of 24.3(range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival(OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement(P = 0.023), stenosis at diagnosis(P < 0.0001), and occurrence of post-RT stenosis or TEF(P < 0.001) in univariate analysis, while stenosis at diagnosis(P = 0.004) and occurrence of post-RT stenosis or TEF(P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.

Impact of simultaneous assay, the PCNA, cyclinDl, and DNA content with specimens before and after preoperative radiotherapy on prognosis of esophageal cancer-possible incorporation into clinical TNM staging system

AIM: The aim of the present study is to use immunohisto chemical methods to investigate the clinical implications of tumor markers in esophageal squamous cell carcinoma and evaluate their impact on prognosis. METHODS: From November 1990 to December 1996, 47 patients were treated with preoperative radiation followed by radical esophagectomy. All patients were confirmed pathologically as suffering from squamous cell carcinoma. Immunohistochemical stain was done for PCNA, cyclinDl protein expression and DNA content analyzed by image cytometry. Kaplan-Meier method for single prognostic factor and log-rank test was used to test the significant difference. Cox stepwise regression model and prognosis index model were used for survival analysis with multiple prognostic factors. RESULTS: Radio-pathological change, T stage and N stage, as the traditional prognostic factors had statistical difference in 3-, 5- and 10-year survival rates. While, tumor cell proliferating marked PCNA, cyclinDl and DNA content served as independent prognostic factors of esophageal carcinoma. There was definitely an identity between the single and multiple factor analyses. PI was more accurate to evaluate the prognosis of esophageal carcinoma. CONCLUSION: It is possible that tumor cell proliferating marked PCNA, cyclinD1 and DNA content would become the endpoints for evaluating the prognosis of esophageal carcinoma.

Value of long non-coding RNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy

BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.

Changes of serum p53 antibodies and clinical signifi cance of radiotherapy for esophageal squamous cell carcinoma

AIM： To explore the relationship between serum p53 antibodies （p53-Abs） and clinicopathological characteristics and therapeutic effect in patients with esophageal carcinoma （EC）, and to investigate sequential changing regularity of serum pS3-Abs after radiotherapy. METHODS： The serum pS3-Ab levels were detected in 46 EC patients and 30 healthy adults by enzyme linked immunosorbent assay （ELISA）. The blood samples were collected on the day before radiotherapy and on the administration of an irradiation dose of 20 Gy/10 f/12 d, 40 Gy/20 f/24 d and 60 Gy/30 f/36 d after radiotherapy. RESULTS： The level and positive rate of serum pS3-Abs in EC patients were significantly higher than those in normal individuals （P 〈 0.05）. Serum anti-p53 antibodies were positive in 18 of 46 EC patients （39.1%）. The positive rate of pS3-Abs in EC was related to histological grade, disease stage and lymph node metastasis （P 〈 0.05）, but it was not significantly related to sex, age and to the size and site of tumor. The level and positive rate of p53-Abs had significant differences between before radiotherapy and after administration of an irradiation dose of 40 Gy/20 f/24 d and 60 Gy/30 f/36 d （P 〈 0.05 orP 〈 0.01）. The positive rate of p53-Abs in EC patients with effect was significantly lower than that in those without effect after radiotherapy （P 〈 0.0001）.CONCLUSION： Detection of serum p53-Abs is helpful to the diagnosis of esophageal carcinoma. Monitoring for sequential change of serum p53-Abs before and after radiotherapy in patients with esophageal carcinoma is also useful to evaluate the response to the treatment and prognosis of the patients.

Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients:A phaseⅡclinical trial

Objective:To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma(EC).Methods:Eligible patients were aged 70 years or older and had treatment-naive,histologically proven inoperable locally advanced EC.Enrolled patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions,concurrent with weekly infusion of nimotuzumab.The primary end point was the rate of more than grade 3 toxicities.Results:From June 2011 to July 2016,46 patients with stageⅡ-IV EC with a median age of 76.5 years were enrolled.There were 10,28 and 8 patients with stageⅡ,III and IV disease,respectively.The common acute toxicities included esophagitis(grade 1-2,75.4%;grade 3,8.7%),pneumonitis(grade 1,4.3%;grade 2,6.5%;grade3,2.2%),leukopenia(grade 1-2,60.9%;grade 3-4,4.4%),gastrointestinal reaction(grade 1-2,17.3%;grade 3,2.2%),thrombocytopenia(grade 1-2,21.7%;grade 3,2.2%),and radiothermitis(grade 1-2,39.2%).The incidence of grade 3-4 adverse effects was 17.4%.No grade 5 toxicities were observed.Clinical complete response,partial response,stable disease,and progressive disease were observed in 1(2.2%),31(67.4%),12(26.1%),and 2(4.3%)patients,respectively.The median overall survival(OS)and progression-free survival(PFS)were 17 and 10 months,respectively.The 2-,3-,and 5-year OS and PFS rates were 30.4%,21.7%,19.6%,and 26.1%,19.6%,19.6%,respectively.Conclusions:Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical candidates.Further studies are warranted to confirm its therapeutic effects in elderly EC patients.

Association of insulin-like growth factor-binding protein-3 with radiotherapy response and prognosis of esophageal squamous cell carcinoma

Background: Insulin?like growth factor?binding protein?3(IGFBP?3) is suggested to predict the radiosensitivity and/or prognosis of patients with esophageal squamous cell carcinoma(ESCC). The present study was designed to investi?gate the clinical and prognostic efects of IGFBP?3 on ESCC.Methods: IGFBP?3 was detected by immunohistochemistry in parain?embedded tissues from 70 ESCC patients treated with radiotherapy alone and further examined by western blotting analysis in 10 pairs of fresh ESCC tissues and adjacent non?malignant esophageal specimens. Receiver operating characteristic(ROC) analysis was used to determine cut?of scores for tumor positivity and to evaluate patient survival status. The χ2 test was performed to analyze the association of IGFBP?3 expression with clinical characteristics and radiotherapy response. Associations between prognostic outcomes and IGFBP?3 expression were investigated using Kaplan–Meier analysis and the Cox proportional hazards model.Results: The threshold for IGFBP?3 positivity was set to greater than 65% [area under the ROC curve(AUC)(45.7%) were deined as having high IGFBP?3 expression= 0.690, P < 0.019]. Of the 70 ESCC patient tissues tested, 32. The levels of IGFBP?3 protein expression were decreased in 70.0%(7 of 10) of ESCC tissues compared with adjacent non?malignant esophageal tissue. In addition, IGFBP?3 expression was associated with pathologic classiication(P < 0.05 for T, N, and M categories and clinical stage). Patients with elevated protein level of IGFBP?3 in the tumor had an improved radiotherapy response and prolonged overall survival(P < 0.001).Conclusions: High level of IGFBP?3 expression in ESCC associates with early clinical stages and are predictive for favorable survival of the patients treated with radiotherapy.

Treatment guideline of radiotherapy for Chinese esophageal carcinoma (draft)

Esophageal carcinoma is one of the most common human cancers in China. Radiotherapy plays an important role in combination therapy of esophageal carcinoma. With regret, there is still no unified standard for the treatment of esophageal carcinoma in China, and there are many controversies in the treatment regimens, indications, methods and efficacy. Clinically, the clinical practice guidelines of the National Comprehensive Cancer Network (NCCN) of the United States were often consulted, but the data of them were mainly from the patients from Europe and America, and they might not be applicable for Chinese patients. In order to standardize clinical process of radiotherapy for esophageal carcinoma in China, the Esophageal Carcinoma Cooperative Group of Radiation Oncology Society of Chinese Medical Association wrote a consensus and controversies on the radiotherapy for esophageal carcinoma (draft) after years of research and discussion. We hope it be tried out and discussed with advice and valuable suggestions, in order to accelerate the process of standardization of esophageal carcinoma treatment in China.

Neoadjuvant chemoradiotherapy for esophageal cancer:Impact on extracapsular lymph node involvement

AIM:To assess the effects of neoadjuvant chemoradiotherapy(CRT) on the presence of extracapsular lymph node involvement(LNI) and its prognostic value in patients with resected esophageal cancer.METHODS:Two hundred and ninety-eight patients with advanced esophageal cancer underwent esophagectomy between 1997 and 2006.One hundred and ninety patients(63.8%) were treated with neoadjuvant CRT prior to resection.A total of 986 metastatic LNs were examined.Survival of the patients was analyzed according to intra-and extra-capsular LNI.RESULTS:Five-year survival rate was 22.5% for the entire patient population.Patients with extracapsular LNI had a 5-year survival rate of 16.7%,which was comparable to the 15.8% in patients with infiltrated nodes of the celiac trunk(pM1lymph).In contrast to patients treated with surgery alone,neoadjuvant therapy resulted in signif icantly(P = 0.001) more patients with pN0/M0(51.6% vs 25.0%).In 17.6% of the patients with surgery alone vs 16.8% with neoadjuvant CRT,extracapsular LNI was detected.Neoadjuvant therapy does not reduce the occurrence of extracapsular LNI.CONCLUSION:Extracapsular LNI is an independent negative prognostic factor not influenced by neoadjuvant CRT.In a revised staging system for esophageal cancer,extracapsular LNI should be considered.

Neoadjuvant chemoradiotherapy plus surgery in the treatment of potentially resectable thoracic esophageal squamous cell carcinoma

BACKGROUNDIn recent years, neoadjuvant chemoradiotherapy (NCRT) combined with surgeryhas been gradually applied in patients with locally advanced thoracic esophagealcancer, but its effectiveness and safety remains unclear. In this clinical trial, weprospectively investigated the efficacy and safety of NCRT plus surgery in thetreatment of thoracic esophageal squamous cell carcinoma (TESCC).AIMTo investigate the efficacy and safety of NCRT combined with surgery in thetreatment of potentially resectable TESCC.METHODSThirty patients with advanced TESCC hospitalized in our hospital from July2016 to June 2019 were prospectively studied. All patients received NCRT, whichincluded intensity modulated conformal radiotherapy (40-44 Gy/20-22f, 2 Gy/f)and chemotherapy (paclitaxel 150-175 mg/m2d1, 22 + lobaplatin 25-30 mg/m2d2,23 for two cycles). Surgery was performed after radiotherapy and chemotherapy.The effectiveness and safety of these treatments were observed.RESULTSAmong these 30 patients, complete response was achieved in two cases (6.7%) andpartial response in 26 cases (86.7%), yielding an objective response rate of 100%.All patients underwent radical surgery successfully. The R0 resection rate was100%, and the pathologic complete response rate was 33.3%. The incidence ofgrade III- IV granulocytopenia was 10% during the NCRT, and anastomoticleakage occurred in one patient after surgery.CONCLUSIONFor patients with potentially resectable TESCC, NCRT can effectively reduce thetumor size, increase R0 resection rate, and achieve obvious pathologicaldegradation, with mild adverse reactions. Thus, it is worthy of wider clinicalapplication.

Literature analysis of radiotherapy for esophageal cancer in China

Background and Objective: Many patterns of treatment have been used to treat esophageal carcinoma in the past years, however, an optimal treatment is still the key issue to be explored. Therefore, we analyzed the published literature about radiotherapy for esophageal cancer in recent 15 years in China, and observed the survival rate, local control rate, adverse events, and so on. Methods: A total of 56 eligible papers about radiotherapy for esophageal squamous cell carcinoma published in Chinese core periodicals between 1994 and 2009 were selected. The survival rates, local control rates, and adverse events were analyzed. Results: The 1-, 2-, 3-, and 5-year overall survival rates of the patients reported in the 56 papers were (67.99 ± 12.55)%, (49.59 ± 11.79)%, (34.50 ± 11.49)%, and (23.31 ± 10.21)%, respectively. The 1-, 2-, 3-, and 5-year local control rates were (73.04 ± 13.37)%, (61.60 ± 15.50)%, (51.77 ± 15.00)%, and (50.15 ± 21.36)%, respectively. The acute esophageal toxicity rate was (44.84 ± 25.71)% in 32 papers reported in recent 15 years, and the acute esophageal toxicity over grade II accounted for (35.93 ± 22.90)%. The rates of acute esophageal toxicity were (26.84 ± 13.12)% for conventional radiation, (53.72 ± 21.82)% for late course accelerated hyperfractionation radiation, (61.33 ± 28.69)% for concurrent chemoradiotherapy, and (40.31 ± 27.22)% for other ways of radiation. The late toxicity rate described in 23 papers was (5.13 ± 4.07)% in recent 15 years. The late toxicity rates were (5.66 ± 3.42)% for conventional radiation, (4.53 ± 4.07)% for late course accelerated hyperfractionation radiation, (2.24 ±1.31)% for concurrent chemoradiotherapy, and (7.34 ± 5.06)% for other ways of radiation. The Meta analysis indicated that concurrent chemoradiotherapy was better than late course accelerated hyperfractionation radiation and conventional radiation. Conclusions: The long-term survival of patients with esophageal cancer is still disappointed in recent years. Concurrent chemoradiotherapy shows advantages in treating esophageal cancer and, currently, is the best non-surgical treatment of esophageal cancer.