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Objective:To discuss the effect of downregulating the proline-rich protein 11(PRR11)expression on drug resistance of the esophageal cancer drug resistant cells,and to clarify the related mechanism.Methods:The drug resistant cells EC9706/cisplatin(DDP)were established by incrementally stimulating the human esophageal cancer EC9706 cells with the increasing concentrations of DDP.The drug sensitivity of the EC9706/DDP cells was detected by MTT assay;the expression levels of PRR11 mRNA and protein in the EC9706/DDP cells and their parent EC9706 cells were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.The EC9706/DDP cells were divided into control group,sh-NC group(infected with sh-NC),sh-PRR11 group(infected with sh-PRR11),sh-NC+DDP group(infected with sh-NC and treated with 4 mg·L-1 DDP),and sh-PRR11+DDP group(infected with sh-PRR11 and treated with 4 mg·L-1 DDP).The expression levels of PRR11 mRNA in the cells in various groups were detected by RT-qPCR method;the expression levels of PRR11,phosphoinositide 3-kinase(PI3K)p110α,protein kinase B(AKT),phosphorylated AKT(p-AKT),P-glycoprotein(P-gp),and multidrug resistance-associated protein 1(MRP1)proteins in the cells in various groups were detected by Western blotting method;the apoptotic rates of the cells in various groups were detected by flow cytometry.Results:The DDP-resistant cell line EC9706/DDP was successfully obtained,and the drug resistance index was 7.23±0.86.Compared with the EC9706 cells,the expression levels of PRR11 mRNA and protein in the EC9706/DDP cells were increased(P<0.05).Compared with control and sh-NC groups,the expression levels of PRR11 mRNA and protein in the cells in sh-PRR11 group were decreased(P<0.05),and the 50%inhibitory concentration(IC50)of DDP was decreased(P<0.05).Compared with sh-NC group,the expression levels of PI3K p110α,p-AKT,P-gp,and MRP1 proteins in the cells in sh-NC+DDP and sh-PRR11 groups were decreased(P<0.05),and the apoptotic rate of the cells was increased(P<0.05).Compared with sh-NC+DDP group and sh-PRR11 group,the expression levels of PI3K p110α,p-AKT,P-gp,and MRP1 proteins in the cells in sh-PRR11+ DDP group were increased(P<0.05),and the apoptotic rate of the cells was increased(P<0.05).Conclusion:Downregulating the expression of PRR11 gene in the drug resistant EC9706/DDP cells can inhibit the expressions of drug resistance-related proteins,reverse the resistance to DDP,and induce the apoptosis;its mechanism may be related to the inhibition of activation of the PI3K/AKT signaling pathway.
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Objective:To understand the current status of self-management positivity of postoperative patients with esophageal cancer and to analyze its influencing factors.Methods:From August 2022 to September 2023, 158 postoperative patients with esophageal cancer at Sun Yat-sen University Cancer Prevention and Control Center were selected by convenience sampling method, and were investigated using a general information questionnaire, Patient Activation Measure (PAM), Fear of Progression Questionnaire Short Form (FOP-Q-SF), and Family APGAR Index (IAPGAR) for a cross-sectional survey, and multiple linear regression was used to analyze the influencing factors of the self-management positivity in patients with postoperative esophageal cancer.Results:Totally 144 questionnaires were effectively collected, of which 106 males and 38 females, with 22 cases aged 18-39 years old, 55 cases aged 40-59 years old, and 67 cases aged ≥ 60 years old. Totally 144 patients scored (59.61 ± 16.07) points on the PAM, (40.45 ± 9.76) on the FOP-Q-SF, and (11.41 ± 2.36) on the IAPGAR, and the results of the multiple linear regression analysis showed that the literacy level, fear of disease progression, and family caring index were the influencing factors of the positivity of the patients′ self-management after the surgery of esophageal cancer ( t=2.54, -13.49, 2.45, all P<0.05). Conclusions:There is always room for improvement in the degree of active self-management of postoperative patients with esophageal cancer. Clinical care workers should pay close attention to the current status of self-management positivity of postoperative patients with esophageal cancer, and formulate a systematic, scientific, and effective intervention strategy for self-management positivity.
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The current recommendation for postoperative radiotherapy for esophageal cancer in China is mainly based on the data of incomplete two-field dissection of open left thoracotomy. At present, the type of surgery for esophageal cancer gradually transitions from open left thoracotomy to open right thoracotomy and from open esophagectomy to minimally invasive esophagectomy (MIE). Patients with early-stage esophageal cancer are selected as candidates for MIE. MIE is less invasive than open esophagectomy, and the right thoracic approach is conducive to more thorough lymph node dissection. However, few data and related studies are available on the patterns of failure after MIE in esophageal cancer, and guiding an adjuvant therapy is difficult. The feasibility of an adjuvant therapy for selective high-risk patients and the optimized treatment after MIE remains to be explored in clinical practice. In this regard, this article aims to review the safety of MIE, long-term survival outcomes, postoperative recurrence patterns, and recurrence rates of patients to discuss the value of postoperative adjuvant therapy and guide clinical treatment.
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Objective:To analyze applications of different level of exercise intensity in patients with esophageal cancer during concurrent chemoradiotherapy.Methods:By convenient sampling method, a total of 120 patients with esophageal cancer during concurrent chemoradiotherapy were adopted in Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Sciences from April 2019 to October 2020, they were assigned to control group, primary degree group, intermediate degree group and advanced degree group according to the random number table method, with 30 patients in each group. All patients were given routine concurrent chemoradiotherapy nursing care, based on this, the primary degree group average walk were 5 000 - 7 499 steps/d, intermediate degree group were 7 500 - 9 999 steps/d, advanced degree group were 10 000 - 12 499 steps/d, besides, the control group did not require the amount of walking. Before and three, six weeks after therapy, the intervention effect was assessed by Scored Patient-Generated Subjective Global Assessment (PG-SGA), BMI, serum total protein, albumin as well as the Revised Piper Fatigue Scale (PFS-R).Results:After six months of therapy, the scores of PG-SGA were (4.31 ± 1.47) and (4.15 ± 1.46) in the intermediate degree group and advanced degree group, lower than in the primary degree group and control group (5.46 ± 1.88) and (5.96 ± 1.91), the differences were statistically significant ( t values were 2.57-3.98, all P<0.05); the levels of serum total protein and albumin were (54.45 ± 10.58), (33.72 ± 7.19) and (55.19 ± 9.82), (34.00 ± 6.52) g/L in the intermediate degree group and advanced degree group, higher than in the primary degree group and control group (49.11 ± 7.71), (29.61 ± 6.21) and (48.04 ± 8.40), (30.04 ± 6.13) g/L, the differences were statistically significant ( t values were 2.19-2.88, all P<0.05). After three and six months of therapy, the scores of PFS-R were (3.41 ± 0.57), (4.62 ± 0.73) in the intermediate degree group, lower than in the primary degree group, advanced degree group and control group (4.25 ± 0.89), (5.43 ± 0.69), (4.19 ± 0.79), (6.11 ± 0.93) and (4.14 ± 0.59), (5.39 ± 0.79) ( t values were 4.01-8.63, all P<0.05). Conclusions:7 500 - 9 999 steps/d are optimal walking exercise intensity, it can effectively improve the nutritional status and reduce fatigue of patients with esophageal cancer during concurrent chemoradiotherapy.
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Objective:To explore a new technique for lung dose reduction in esophageal cancer radiotherapy based on the dose distribution characteristics of the half-field combined with intensity-modulated radiotherapy (IMRT) technique.Methods:A three-dimensional water tank was used to measure the dose distribution at the edge of the symmetrical field and half-field, which was then compared and analyzed. Twenty patients with the middle and lower thoracic esophageal cancer receiving radiotherapy with prescription doses of 50.4-60.0 Gy were selected. Based on the Varian Vital beam linear accelerator and Eclipse planning system, flattening filter (FF) technique symmetrical field and half-field beam design and the flattening filter-free (FFF) technique symmetrical field and half-field design were adopted to compare and analyze various dose data and treatment MU numbers for the target area and the endangered organs. The field settings were chosen in the front 1 and back 4 mode.Results:Compared with the symmetrical field plan, the half-field plan significantly improved the irradiated dose to the lung with a statistically significant difference ( P<0.05), and the half-field FFF was slightly better than the half-field FF mode. Compared with the total lung V 5Gy, V 20Gy, V 30Gy, and D mean dosimetric parameters (Gy), the FF symmetric field and FFF half-field were (49.64±5.39)% vs.(42.70±5.53)%, (15.99±3.93)% vs.(13.32±3.06)%, (9.24±2.77)% vs.(8.50±2.62)%, and (10.45±1.76)% vs.(9.50±1.53)%, respectively. There was a significant reduction in the volume dose values for all structures of the lung (all P<0.05). For other comparative data, the irradiated dose for the heart of the symmetrical field was better than that of the half-field mode ( P<0.05), and the differences in conformity index (CI) and homogeneity index (HI), number of treated MU, and spinal cord associated with the target area were not statistically significant (all P>0.05). Conclusions:During radiotherapy for esophageal cancer, target area coverage and dose volume data of the lung are the main parameters affecting the efficacy and side effects. IMRT treatment based on the half-field mode can give full play to the advantages of half-field and IMRT, and significantly improve the irradiated dose to the lung, which can offer an additional clinical option.
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Objective:To investigate the recurrence-free survival (RFS) and influencing factors of intensity-modulated radiotherapy±chemotherapy (IMRT±C) for the upper thoracic esophageal cancer.Methods:The medical records of 168 patients with cervical and upper thoracic esophageal cancer who met the inclusion criteria from January 2011 to December 2015 were retrospectively analyzed. The RFS was calculated by the Kaplan-Meier method. Multivariate prognostic analysis was performed by Cox models. The recurrence factors were identified by the Logistics model. Results:The 1-, 3-, and 5-year RFS rates were 67.8%, 38.0%, and 20.4%, respectively, and the median RFS was 21.9 months. The locoregional recurrence rate was 47.6%(80/168). The recurrence sites were local esophagus ( n=63), regional lymph nodes ( n=7), and local esophagus+ regional lymph node recurrence ( n=10). Multivariate analysis showed that hoarseness, cTstaging, combined with chemotherapy, 95%PTV 1 exposure dose and GTV average exposure dose were the influencing factors of RFS ( P=0.029, <0.001, 0.031, 0.038, 0.020). Logistics model showed that cTstaging, cNstaging, short-term efficacy, irradiationmethod, GTV maximum transverse diameter and PTV average exposure dose were the influencing factors of recurrence ( P=0.046, 0.022, 0.001, <0.001, 0.012, 0.001). Conclusions:Patients with cervical and upper thoracic esophageal cancer treated with radical IMRT combined with/without chemotherapy have a higher locoregional recurrence rate, and the recurrence rate is mainly the esophagus. The independent factors that affect RFS are different from the risk factors of recurrence.
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Objective:To investigate the prognostic factors of patients with esophageal squamous cell carcinoma with pulmonary metastasis.Methods:Clinical characteristics of 135 esophageal squamous cell carcinoma patients presenting with pulmonary metastasis after treatment in Zhejiang Cancer Hospital from 2008 to 2018 were retrospectively analyzed. Thesurvival rate was calculated by Kaplan-Meier method. Univariate analysis was performed by log-rank test. Multivariate prognostic analysis was conducted by Cox models.Results:The median follow-up time of 135 patients with esophageal squamous cell carcinoma was 94.2 months (19.5-258.9 months), and 109 patients died (80.7%). The 1-and 2-year overall survival rates were 47.4% and 25.1%, with the median survival time was 11.1 months (7.3-14.9 months). Univariate prognostic analysis showed that age, number of lung metastases, treatment of lung metastases, lymph node metastasis, distant organ metastasis, and the interval between the first treatment and lung metastasis were the prognostic factors of esophageal squamous cell carcinoma with lung metastasis (all P<0.05). Multivariate analysis demonstrated that age and number of lung metastases were the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases (all P<0.05). Conclusions:Age and number of lung metastases are the independent prognostic factors for patients with esophageal squamous cell carcinoma with lung metastases. Surgery or radiotherapy-based regional therapy can enhance clinical prognosis.
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Objective:To compare the setup errors in the supraclavicular regions of two different postures (arms placed on each side of the body, namely the body side group; arms crossed and elbows placed above forehead, namely the uplifted group) using the chest and abdomen flat frame fixation device in lung and esophageal cancer.Methods:Clinical data of patients with stage Ⅰ to Ⅳ lung or esophageal cancer who received three-dimensional radiotherapy with chest and abdomen flat frame fixation device in our institution from November 2020 to April 2021 were retrospectively analyzed. The setup errors of two postures were compared.Results:A total of 56 patients were included, including 31 patients (55%) in the body side group and 25 patients (45%) in the uplifted group. A total of 424 CBCTs were performed in the whole group. The overall setup errors in the X, Y and Z directions were similar in both groups ( P>0.05). The setup errors of sternoclavicular joint in the X and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.163±0.120) cm vs. (0.209 ±0.152) cm, P=0.033; 0.715°±0.628° vs. 0.910°±0.753°, P=0.011]. The setup errors of acromioclavicular joint in the Y, Z and RZ directions in the body side group were significantly smaller than those in the uplifted group [(0.233±0.135) cm vs. (0.284±0.193) cm, P=0.033; (0.202±0.140) cm vs. (0.252±0.173) cm, P=0.005; 0.671°±0.639° vs. 0.885°±0.822°, P=0.023]. The margins of target volume for setup errors were smaller in the X (0.45 cm vs. 0.54 cm) and Y (0.54 cm vs. 0.65 cm) directions of the sternoclavicular joint, as well as in the Y (0.59 cm vs. 0.78 cm) and Z directions (0.53 cm vs. 0.72 cm) of the acromioclavicular joint in the body side group. Conclusions:For lung and esophageal cancer patients requiring supraclavicular irradiation, the body side group yields smaller setup errors and corresponding margins of target volume than the uplifted group. In clinical practice, it is necessary to take comprehensive consideration of the accuracy of radiotherapy and additional radiation of the limbs to select appropriate posture.
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Esophageal cancer is a malignant tumor of the digestive system that has a high incidence in China. The traditional treatment methods include surgery, radiotherapy, and chemotherapy, but the long-term efficacy is not good and the side effects are obvious. As a traditional physical therapy, hyperthermia has no significant toxic and side effects. Studies have shown that hyperthermia can increase the sensitivity of esophageal cancer to radiotherapy and chemotherapy, and its combined use in the treatment of esophageal cancer can prolong the survival and improve the quality of life. In addition, the innovation of materials and technologies brings new breakthroughs to tumor hyperthermia.
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China is a country with high incidence of esophageal cancer. In recent years, with the deepening research, the value of neoadjuvant therapy in locally advanced resectable esophageal cancer has been widely approved by clinicians, compared with surgery alone or adjuvant therapy. However, the survival results of different neoadjuvant therapy options may be quite different, and many problems remain unresolved. In this article, a systemic literature review was carried out to summarize the radiotherapy target, radiotherapy dose, chemotherapy regimen of neoadjuvant chemoradiotherapy and time to surgery, as well as review the research status and progress on targeted therapy and immunotherapy as neoadjuvant therapy for esophageal cancer.
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Esophageal squamous cell carcinoma (ESCC) is the most predominant pathological type of esophageal cancer in China. In recent years, with the development of molecular targeted drugs, targeted therapy has become a hot research topic in the field of ESCC treatment. Nimotuzumab is the first humanized monoclonal antibody targeting epidermal growth factor receptor (EGFR) in China, which has been approved for the treatment of early or locally advanced nasopharyngeal carcinoma. Several phase Ⅱ-Ⅲ clinical trials have explored the use of nimotuzumab in the treatment of ESCC, confirming its significant efficacy and survival benefit in the treatment of advanced ESCC, as well as its favorable safety profile.
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ABSTRACT BACKGROUND: Endoscopic submucosal dissection (ESD) of esophageal superficial neoplasm is associated with a high en bloc R0 resection rate and low recurrence. OBJECTIVE: We aim to compare the performance and clinical outcomes of ESD via ESD after circumferential incision (ESD-C) versus submucosal tunneling (ESD-T). METHODS: Single-center retrospective analysis of all consecutive patients who underwent ESD for superficial esophageal cancer, between 2009 and 2018. ESD-T was defined as the technique of making the mucosal incisions followed by submucosal tunneling in the oral to anal direction. ESD-C consisted of completing a circumferential incision followed by ESD. Main study outcomes included en bloc and R0 resection rates. Secondary outcomes included procedural characteristics, curative resection rate, local recurrence and adverse events. RESULTS: A total of 65 procedures (23 ESD-T and 42 ESD-C) were performed for ESCC (40; 61.5%) and BE-neoplasia (25; 38.5%). There were no statistically significant differences between patients who underwent ESD-T versus ESD-C in en bloc (91.3% vs 100%, P=0.12), R0 (65.2% vs 78.6%, P=0.24), curative resection rates (65.2% vs 73.8%, P=0.47) and mean procedure time (118.7 min with vs 102.4 min, P=0.35). Adverse events for ESD-T and ESD-C were as follows: bleeding (0 versus 2.4%; P=0.53), perforation (4.3% vs 0; P=0.61), esophageal stricture (8.7% versus 9.5%; P=0.31). Local recurrence was encountered in 8.7% after ESD-T and 2.4% after ESD-C (P=0.28) at a mean follow-up of 8 and 2.75 years, respectively (P=0.001). CONCLUSION: ESD-T and ESD-C appear to be equally effective with similar safety profiles for the management of superficial esophageal neoplasms.
RESUMO CONTEXTO: A dissecção endoscópica submucosa (DES) no tratamento da neoplasia superficial do esôfago está associada a uma alta taxa de ressecção R0 em bloco e baixa taxa de recorrência. OBJETIVO: O objetivo deste estudo é comparar o desempenho e os resultados clínicos da DES com incisão circunferencial (DES-C) versus com DES com túnel submucoso (DES-TS). MÉTODOS: Estudo retrospectivo de banco de dados coletados prospectivamente de um centro especializado em DES, investigando pacientes consecutivos submetidos à DES por câncer de esôfago superficial, entre 2009 e 2018. DES-TS foi definida como a técnica de realizar primeiro incisões na mucosa seguida de tunelamento submucoso no sentido oral para anal. DES-C consistiu em completar uma incisão circunferencial seguida da dissecção submucosa. As principais variáveis do estudo incluíram taxas de ressecção em bloco e R0. Os resultados secundários incluíram características do procedimento, taxa de ressecção curativa, recorrência local e eventos adversos. RESULTADOS: Um total de 65 procedimentos (23 DES-TS e 42 DES-C) foram realizados para CCE de esôfago (40; 61,5%) e neoplasia associada ao EB (25; 38,5%). Não houve diferenças estatisticamente significativas entre os pacientes submetidos a DES-TS versus DES-C nas taxas de ressecção em bloco (91,3% vs 100%, P=0,12), R0 (65,2% vs 78,6%, P=0,24), taxas de ressecção curativa (65,2% vs 73,8%, P=0,47) e tempo médio do procedimento (118,7 min com vs 102,4 min, P=0,35). Os eventos adversos para DES-TS e DES-C foram os seguintes: sangramento (0 vs 2,4%; P=0,53), perfuração (4,3% vs 0; P=0,61), estenose esofágica (8,7% vs 9,5%; P=0,31). A recorrência local foi encontrada em 8,7% após DES-TS e 2,4% após DES-C (P=0,28) em um seguimento médio de 8 e 2,75 anos, respectivamente (P=0,001). CONCLUSÃO: DES-TS e DES-C demostram ser igualmente eficazes com perfil de segurança semelhante para o tratamento das neoplasias superficiais do esôfago.
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Humanos , Neoplasias Esofágicas/cirugía , Estenosis Esofágica , Resección Endoscópica de la Mucosa/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia Local de NeoplasiaRESUMEN
Objective:To investigate the value of radiotherapy in patients with stage Ⅳ B thoracic esophageal squamous cell carcinoma (ESCC) at initial diagnosis. Methods:A total of 199 patients with stage Ⅳ B thoracic ESCC at initial diagnosis (according to UICC/AJCC Eighth Edition Esophageal and Esophagogastric Junction Cancer TNM Staging) who were treated in the Fourth Hospital of Hebei Medical University between January 2010 to December 2016 were recruited. Winthin the whole group, 130 patients (65.3%) had distant lymph node metastases alone, 51 cases (25.6%) of solid organ metastases alone and 18 cases (9.0%) of solid organ complicated with distant lymph node metastases. Among them, 16 patients (8.0%) were treated with chemotherapy alone, 50 cases (25.1%) of radiotherapy alone, 133 cases (66.8%) of radiochemotherapy (81 patients treated with concurrent radiochemotherapy and 52 patients treated with sequential radiochemotherapy). The survival rate was calculated by Kaplan-Meier method and the difference was analyzed by log-rank test. Clinical prognosis was assessed by multivariate Cox regression model. Results:The median overall survival (OS) of the entire cohort was 12.3 months (95% CI: 10.6-15.4m), and the 1-, 2-, 3-and 5-year OS rates were 52.1%, 25.2%, 19.1%, and 11.5%, respectively. Multivariate analysis showed that tumor length, the number of metastatic organs, and treatment modalities were the independent prognostic factors for OS. There was no significant difference in OS between concurrent radiochemotherapy and sequential radiochemotherapy ( P=0.955). The OS of patients in the radiotherapy dose of ≥6000 cGy group was significantly longer than that of their counterparts in the 4500-5039 cGy and 5040-6000 cGy groups (both P<0.001). Conclusions:For stage Ⅳ B thoracic ESCC patients at initial diagnosis, tumor length ≤3cm, single organ metastasis, and radiochemotherapy strategy are significantly correlated with longer OS. For stage Ⅳ ESCC patients with good physical status, radiotherapy can be supplemented on the basis of systemic chemotherapy. Concurrent or sequential radiochemotherapy needs to be individualized. If patients are tolerable, radiochemotherapy is recommended to the primary tumor or non-regional metastatic lymph nodes, aiming to prolong the OS of patients.
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Objective:To explore the value of BLADE sequence in determining the target range of esophageal cancer radiotherapy through the correlation and consistency between measured esophageal cancer length on the MRI-BLADE sequence and the surgical pathological specimens.Methods:Clinical data of 36 patients who were pathologically diagnosed with esophageal carcinoma and received preoperative esophageal MRI in the Affiliated Cancer Hospital of Zhengzhou University between January 2016 to June 2019 were collected. The CT, DWI and BLADE sequence images of all participants were collected and imported into the Monaco system, by which the correlation and consistency between the tumor length measured based on these three imaging methods were statistically compared. Furthermore, the differences in gross tumor volume (GTV) delineated by different physicians in different images were compared.Results:The correlation coefficients of the tumor length measured by CT, DWI and BLADE and pathological specimen length were 0.467, 0.723 and 0.896, respectively. The consistency analysis indicated that all the differences between the BLADE sequence and pathological specimen length were within the 95% consistency limit. The consistency and correlation between the BLADE sequence and actual tumor length were significantly better than those between the DWI sequence and CT images (both P<0.05). The volume of DWI and BLADE images obtained by four physicians was significantly smaller than that of CT images (both P<0.05). The differences in GTV delineated by different physicians by these three imaging methods were insignificant (all P>0.05), but the GTV delineated by the four physicians on the BLADE sequence were more similar (all P>0.05). Conclusions:BLADE sequence can help physicians to determine the upper and lower boundaries of esophageal tumors more accurately and reduce the differences in GTV delineation among different physicians. And it can effectively improve the unity of individual′s understanding of the scope of target area delineation, and improve the objectivity of clinicians′ judgment of GTV. BLADE sequence can be used as an important imaging tool for accurate target delineation in radiotherapy.
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Esophageal cancer is a common malignant tumor of digestive system in China. Concurrent chemoradiotherapy has become the widely recognized method for the treatment of inoperable locally advanced esophageal carcinoma. Nevertheless, clinical efficacy of concurrent chemoradiotherapy remains to be enhanced. Nimotuzumab, the first human monoclonal antibody to treat malignant tumors in China, has been applied in the treatment of nasopharyngeal carcinoma, glioma, pancreatic cancer and other malignant tumors, which yields significant survival benefits and causes mild adverse events. Hence, more and more scholars are paying attention to its application value in the treatment of esophageal cancer. In this article, research progress on the application of nimotuzumab in esophageal cancer was reviewed, aiming to provide new ideas for the treatment of esophageal cancer.
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Neoadjuvant chemoradiotherapy is the preferred treatment mode for the diagnosis and treatment of locally advanced operable esophageal carcinoma recommended by many guidelines. However, some problems remain to be further explored. In this article, current problems perplexing clinical practice were sorted out, aiming to provide constructive suggestions for the smooth development of neoadjuvant chemoradiotherapy for esophageal carcinoma in the future.
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The incidence of esophageal cancer ranks third among all malignant tumors in China. Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for locally advanced esophageal cancer. Whether the tumor lesions can achieve complete pathological remission after neoadjuvant chemoradiotherapy provide profound guidance for subsequent treatment. In this article, research progresses on the application of pathological, radiological and biological approaches to evaluate and predict the tumor response to neoadjuvant chemoradiotherapy were reviewed.
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Objective:To explore the genes and molecular markers related to the sensitivity to concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.Methods:The peripheral blood sample of 31 patients with locally advanced esophageal squamous cell carcinoma receiving radical concurrent chemoradiotherapy was collected and the plasma circulating free DNA (cf-DNA) was extracted before treatment. The target gene capture sequencing technology based on NovaseQ6000 high-throughput sequencing platform was employed to detect the changes of target genes and tumor mutation burden (TMB). According to the short-term efficacy of chemoradiotherapy, all patients were divided into the chemoradiotherapy-sensitive group (CR+ PR) and chemoradiotherapy-resistant group (SD+ PD). Bioinformatics and clinical data were adopted to analyze the differences of gene mutation and TMB between two groups.Results:In the sequencing data of 31 patients, the tumor-related genes with a mutation frequency above 10% were Tp53, Notch1, BRAF, FGFR4, CDKN2A, ATRX and Axin2, which were almost equally distributed between the CR+ PR and SD+ PD groups. High-frequency mutant genes were associated with 7 signaling pathways, mainly involved in the RTK/RAS signaling pathways. The TMB value in the CR+ PR group was higher than that in the SD+ PD group ( P=0.04), however, the mutation rate of GXYLT1 and KRT18 genes in the SD+ PD group was higher than that in the CR+ PR group ( P<0.05). Conclusions:Tp53, Notch1 and CDKN2A may be the high-frequency mutant genes associated with the incidence and progression of esophageal squamous cell carcinoma. KRT18, GXYLT1 and TMB are closely correlated with the sensitivity to concurrent chemoradiotherapy of patients with locally advanced esophageal squamous cell carcinoma.
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Objective:To establish a radiomics-based biomarker for predicting pathological response after preoperative neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal cancer.Methods:From 2008 to 2018, 112 patients with locally advanced esophageal cancer who received nCRT were enrolled. All patients were treated with preoperative nCRT combined with surgery. Enhanced CT images and clinical information before nCRT were collected. A lesion volume of interest was manually delineated. In total, 670 radiomics features (including tumor intensity, shape and size, texture and wavelet characteristics) were extracted using the pyradiomics package in PYTHON. The stepwise regression combined with the best subset were employed to select the features, and finally the Logistic regression model was adopted to establish the prediction model. The performance of the classifier was evaluated by the area under the ROC curve (AUC). Results:The pathological complete remission (pCR) rate was 58.0%(65/112). 10 radiomics features were included in the final model, The most relevant radiomics feature was the gray feature (the texture information of the image), followed by the shape and voxel intensity-related features. In the training set, the AUC was 0.750 with a sensitivity of 0.711 and a specificity of 0.778, the corresponding values in the testing set were 0.870, 0.757 and 0.900, respectively.Conclusions:Models based on radiomics features from CT images can be utilized to predict the pathological response to nCRT in esophageal cancer. As it is efficient, non-invasive and economic model, it could serve as a promising tool for individualized treatment when validated by further prospective trials in the future.
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Objective:To investigate the relationship between Onodera′s prognostic nutritional index (PNI) and prognosis of patients with esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy or radiotherapy, aiming to provide a convenient, effective and accurate predictive indicator for evaluating the long-term survival of patients after treatment.Methods:Clinical data of 231 ESCC patients treated with definitive chemoradiotherapy or radiotherapy at the Fourth Hospital of Hebei Medical University from 2013 to 2015 were retrospectively analyzed. The PNI values of each patient at different radiotherapy periods were calculated and the ROC curve was used to determine the optimal cutoff value of PNI before radiotherapy, 231 patients were divided into the better-nourishment group ( n=86) and worse-nourishment group ( n=145). Kaplan- Meier method was used for survival analysis. Cox proportional hazards model was utilized to analyze the relationship between different nutritional status and prognosis. The short-term clinical efficacy and incidence of acute toxicities were statistically compared between two groups. Results:The mean values of PNI before, at week 3, week 6 and 1 month after radiotherapy were48.68±5.08, 39.68±4.87, 43.74±4.89 and48.31±4.92, respectively. The optimal cutoff value of pretreatment PNI was 49.25, the area under the curve (AUC) was 0.655, the sensitivity and specificity were 68.6% and 60.9%, respectively. The 5-year overall survival (OS) and progression-free survival (PFS) rates in the better-nourishment group (PNI≥49.25) were 36.0% and 31.3%, significantly better than 19.3% and 18.6% in the worse-nourishment group (PNI<49.25)( P=0.001, P=0.039). Multivariate analysis showed PNI before the therapy was an independent prognostic factor for OS ( P=0.021). Stratified analysis demonstrated that Stage Ⅰ/Ⅱ and concurrent chemotherapy patients in the better-nourishment group all obtained significantly better OS than their counterparts in the worse-nourishment group ( P=0.007, P=0.004). In addition, the objective response rate in the better-nourishment group was significantly higher than that in the worse-nourishment group ( P=0.047), whereas the incidence of ≥3 grade radiation esophagitis was lower than that in the worse-nourishment group ( P=0.060). Conclusions:Pretreatment PNI is a convenient and reliable indicator for predicting the long-term survival of ESCC patients after definitive chemoradiotherapy or radiotherapy. Patients with higher PNI have relatively better prognosis and radiotherapy tolerance, especially in those with early stage or concurrent chemotherapy.