Critical insights into the "Skeletal muscle volume by 3D imaging and long-term survival in esophageal squamous cell carcinoma with neoadjuvant chemotherapy".

Neoadjuvant chemotherapy (NAC) is commonly administered to improve long-term survival in patients with locally advanced esophageal squamous cell carcinoma (ESCC). This study investigated the impact of perioperative skeletal muscle index (SMI), assessed by 3D imaging, on survival outcomes. We retrospectively reviewed 139 ESCC patients who underwent surgical resection following NAC. SMI was measured pre- and post-NAC using 3D imaging. Patients were stratified into quartiles based on post-NAC SMI, and survival outcomes were evaluated. Patients in the lowest SMI quartile (Q1) were more likely to develop postoperative pneumonia and had significantly worse 3-year overall survival (OS) and relapse-free survival (RFS) compared with those in Q2-Q4 (P < 0.01). Multivariate analysis identified low SMI as an independent predictor of poor OS (HR: 3.22; 95% CI: 1.86-5.57; P < 0.01). Low SMI after NAC, as assessed by 3D imaging, is an independent predictor of poor survival in ESCC patients. These findings highlight the importance of muscle preservation and precise 3D evaluation before surgery.

Objective To explore the predictive value of intravoxel incoherent motion (IVIM) imaging for the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma (ESCC). Methods The prospective study was conducted. The clinicopathological data of 33 patients with locally advanced ESCC who were admitted to Affiliated Hospital of Zhengzhou University from September 2015 to October 2017 were collected. Patients received magnetic resonance imaging (MRI) and IVIM imaging examination before and after neoadjuvant chemotherapy. Two radiologists read the imaging together, manually delineated the region of interest in the diffusion-weighted imaging, and the apparent diffusion coefficient (ADC), diffusion coefficient (D), perfusion coefficient (D*), and perfusion score of the tumor (f) were automatically measured. Patients underwent neoadjuvant chemotherapy with paclitaxel plus cisplatin, and underwent radical surgery for esophageal cancer after 2 cycles of chemotherapy. Observation indicators: (1) comparison of IVIM imaging parameters before and after neoadjuvant chemotherapy in patients with ESCC; (2) comparison of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy in patients with different tumor regression grade (TRG); (3) predictive efficacy of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy for TRG. Measurement data with normal distribution were presented as Mean±SD, and comparison before and after neoadjuvant chemotherapy was done using the paired t test, and comparison between different TRG patients was done using the t test. Measurement data with skewed distribution were presented as M(P25, P75), and comparison before and after neoadjuvant chemotherapy and between different TRG patients were done using the Wilcoxon rank sum test. The receiver operating characteristic (ROC) curve was used to evaluate predictive value of IVIM imaging parameters. Results Thirty-three patients were screened for eligibility, including 26 males and 7 females, aged from 44 to 74 years, with an average age of 60 years. All the 33 patients were diagnosed as ESCC by pathological examination. (1) Comparison of IVIM parameters before and after neoadjuvant chemotherapy in patients with ESCC: 33 patients with ESCC showed a significant difference in the ADC, D, and f value after neoadjuvant chemotherapy [ADC: (1.95±0.56)×10-3 mm2/s vs. (2.54±0.50)×10-3 mm2/s, t=-6.98; D: (1.26×10-3 mm2/s (0.81×10-3 mm2/s, 2.44×10-3 mm2/s) vs. 1.68×10-3 mm2/s (0.83×10-3 mm2/s, 2.27×10-3 mm2/s), Z=-3.96; f: 0.33%±0.14% vs. 0.42%±0.15%, t=-3.13, P<0.05]. (2) Comparison of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy in different TRG patients: of 33 patients, 15 were in TRG 2 and 18 were in TRG 3. The ADC change value, ADC change rate, D change value, D change rate were (0.85±0.52)×10-3 mm2/s, 52.91%±32.51%, 0.64×10-3 mm2/s (0.05×10-3 mm2/s, 1.41×10-3 mm2/s) , 48.20%(3.03%, 16.95%) of TRG 2 patients, and (0.38±0.35)×10-3 mm2/s, 21.94%±19.08%, 0.26×10-3 mm2/s (-1.43×10-3 mm2/s, 0.81×10-3 mm2/s), 20.18%(-58.61%, 77.14%) of TRG 3 patients, respectively, with significant differences between two groups (t=3.09, 3.41, Z=-3.04, -2.93, P<0.05). (3) Predictive efficacy of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy for TRG: ROC curve analysis showed that ADC change value exhibited an area under curve (AUC) of 0.798, a sensitivity of 66.7% and a specificity of 94.4% in predicting TRG, when 0.86×10-3 mm2/s was used as the cut-off value. With 43.3% as the cut-off value, ADC change rate had an AUC of 0.793, a sensitivity of 66.7% and a specificity of 88.9% in predicting TRG. With 0.35×10-3 mm2/s as the cut-off value, D change value had an AUC of 0.809, a sensitivity of 73.3% and a specificity of 77.8% in predicting TRG. With 25.9% as the cut-off value, D change rate had an AUC of 0.800, a sensitivity of 80.0% and a specificity of 72.2% in predicting TRG. Conclusions The change value and change rate of ADC and D values before and after neoadjuvant chemotherapy are potential predictors of pathologic response in ESCC. The significantly increased ADC and D values after neoadjuvant chemotherapy are prone to good pathologic response. The change value and change rate of D values show a better predictive value for pathologic response to neoadjuvant chemotherapy in ESCC compared with those of ADC values. Key words: Esophageal neoplasms; Esophageal cancer; Magnetic resonance imaging; Intravoxel incoherent motion; Diffusion weighted imaging; Neoadjuvant chemotherapy

Neoadjuvant therapy followed by surgery is a standard treatment for locally advanced oesophageal cancer. However, the roles of neoadjuvant chemoradiotherapy and chemotherapy in treating oesophageal cancer remain controversial. In this comprehensive meta-analysis, we examine the efficacy of adding radiotherapy to neoadjuvant chemotherapy for treating oesophageal cancer as reported in qualified randomized controlled trials (RCTs). We conducted a systematic literature search using PubMed, Embase, Cochrane Library databases, Google Scholar and the American Society of Clinical Oncology database to identify relevant studies up to 31 March 2016. Data including the pathological complete response rate, R0 resection rate and 3-year survival rate were extracted and analysed. Five qualified RCTs were included with a total of 709 patients. Meta-analysis showed that neoadjuvant chemoradiotherapy significantly increases the rates of pathological complete response and R0 resection in patients with oesophageal adenocarcinoma or squamous cell carcinoma (SCC). However, we found a significantly increased 3-year survival rate only in oesophageal SCC patients treated with neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy (56.8 and 42.8%, respectively); relative risk (RR): 1.31 [95% confidence interval (CI) 1.10-1.58, P = 0.003]. In oesophageal adenocarcinoma patients, no significant survival benefit of neoadjuvant chemoradiotherapy was found compared with neoadjuvant chemotherapy alone (46.3 and 41.0%, respectively; RR: 1.13, 95% CI 0.88-1.45, P = 0.34). Our meta-analysis adds to the evidence showing that neoadjuvant chemoradiotherapy should be the standard preoperative treatment strategy for locally advanced oesophageal SCC. For oesophageal adenocarcinoma, neoadjuvant chemotherapy alone may be the best preoperative treatment strategy to avoid the risk of adverse effects of radiotherapy.

The aim of this study was to quantify changes in body composition during ovarian cancer treatment and relate these changes to rates of complete gross resection (CGR). One hundred two patients with stage III or IV ovarian cancer who underwent neoadjuvant chemotherapy (NACT) followed by interval debulking surgery were a part of a prospectively collected database that included computed tomography scans at three time points-diagnosis, following NACT, and following debulking surgery. Skeletal muscle, visceral adipose, and subcutaneous adipose tissue volumes were obtained from a 30-mm volumetric slab beginning at the third lumbar vertebrae. Following NACT, skeletal muscle volume was significantly reduced (352.5 to 335.0 cm3, P < 0.001), whereas adiposity was unchanged. Body mass index (BMI) and skeletal muscle volume were significantly lower in patients who achieved CGR (P < 0.05). When these patients were stratified by BMI, the significant association of skeletal muscle to CGR was limited to patients with a BMI < 25 kg/m2 (P = 0.007). Skeletal muscle volume was significantly reduced in patients undergoing NACT for ovarian cancer. Non-overweight patients were more likely to achieve CGR if they had lower skeletal muscle volume. Use of volumetric-based measurement for ascertaining body composition should be explored further.

Esophagectomy postallogenic hematopoietic stem cell transplantation for hematologic malignancy: A case series

&lt;div&gt;Abstract&lt;p&gt;The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (&lt;i&gt;n&lt;/i&gt; = 33) or did not receive NAC (&lt;i&gt;n&lt;/i&gt; = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163&lt;sup&gt;+&lt;/sup&gt; TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163&lt;sup&gt;+&lt;/sup&gt; TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC.&lt;/p&gt;Implications:&lt;p&gt;The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.&lt;/p&gt;&lt;/div&gt;

&lt;div&gt;Abstract&lt;p&gt;The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (&lt;i&gt;n&lt;/i&gt; = 33) or did not receive NAC (&lt;i&gt;n&lt;/i&gt; = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163&lt;sup&gt;+&lt;/sup&gt; TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163&lt;sup&gt;+&lt;/sup&gt; TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC.&lt;/p&gt;Implications:&lt;p&gt;The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.&lt;/p&gt;&lt;/div&gt;

The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC. IMPLICATIONS: The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.

Objective To assess intravoxel incoherent motion(IVIM) in evaluating and predicting response to neoadjuvant chemotherapy(NAC) in esophageal squamous cell carcinoma(ESCC). Methods Forty-seven patients with ESCC diagnosed by pathological findings on biopsy from September 2015 to March 2017 were prospectively collected. All patients were examined before and after NAC using routine MRI scan and IVIM. The standard apparent diffusion coefficient (ADCstandard), diffusion coefficient (D), perfusion coefficient (D*) and perfusion score (f) were measured. The patients were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) according to the 1.1 version of the response evaluation criteria in solid tumors (RECIST). Thirty-one patients underwent surgery after NAC, and the patients were divided into TRG 0-3 according to tumor regression grade (TRG). The differences of parameter values before and after NAC between different groups were analyzed using Student's t test (normal distribution) and Wilcoxon rank sum tests (non-normal distribution). The parameters with statistical significance were evaluated by the receiver operating characteristics (ROC) curves. Results The ADCstandard values before and after NAC were (1.97±0.51) ×10-3, (2.42±0.52)×10-3 mm2/s. The D values before and after NAC were (1.30±0.30)×10-3, (1.63±0.35)×10-3 mm2/s. The ADCstandard and D values after NAC were significantly higher than those before NAC, and the differences were statistically significant (t=-6.35, -5.25 respectively, both P 0.05). The patients were divided into PR group (29 cases) and SD group (18 cases) after NAC, without CR and PD patients. The ADCstandard, D and f values of PR group were significantly lower than those of the SD group before NAC (t=-3.11, -2.53 and -2.10 respectively, all P<0.05). The ADCstandard, D, D* and f values after NAC revealed no significant difference between PR and SD groups. Thirty-one patients received operation after NAC, which were divided into TRG 2 group (14 cases) and TRG 3 group (17 cases) according to TRG standard, without TRG 0 and TRG 1 patients. All the parameter values before NAC revealed no significant difference between TRG 2 and TRG 3 groups. The D values after NAC in TRG 2 and TRG 3 groups were (1.81±0.31)×10-3, (1.46±0.39)×10-3 mm2/s respectively, and the significant difference was found between two groups (t=2.76, P<0.05). The efficiency of efficacy evaluation for NAC was the highest at D value of 1.68×10-3 mm2/s, with sensitivity and specificity being 85.7% and 70.6%, respectively. Conclusion IVIM can be used as a new imaging method to evaluate and predict the efficacy of NAC for ESCC, among which the parameter D was the most valuable. Key words: Esophageal neoplasms; Magnetic resonance imaging; Intravoxel incoherent motion; Neoadjuvant chemotherapy

Unravelling the difference of immune microenvironment characteristics between esophageal basaloid squamous cell carcinoma and conventional esophageal squamous cell carcinoma.

The prognosis of patients with esophageal cancer is associated with nutrition. The aim of the present study was to investigate the effect of thoracic status on the prognosis of elderly patients with esophageal squamous cell carcinoma (ESCC) following radiotherapy. A retrospective analysis was performed of 123 elderly patients who underwent radiotherapy for ESCC and were admitted to The Affiliated Hospital of Xuzhou Medical University (Xuzhou, China) between October 2018 and October 2021. General clinical data and hematological data of the patients were collected before radiotherapy, with CT delineation of the 10-segment thoracic skeletal muscle volume by radiotherapy. The 10th thoracic vertebra level skeletal muscle volume index (T10 SMVI)=T10 skeletal muscle volume (cm3)/height2 (m2). By dividing the patients according to the optimal cutoff value (using X-tile 3.6.1) into the T10 sarcopenia group and the T10 non-reduced skeletal muscle group (T10 non-sarcopenia group), intergroup comparisons were performed. The area under the curve was calculated from the receiver operating characteristic curve (ROC) to assess the prediction ability of T10 SMVI, the prognosis nutrition index (PNI) and the geriatric nutrition risk index (GNRI) for survival outcomes. Survival curves were drawn using the Kaplan-Meier method, and risk factors affecting progression-free survival (PFS) and overall survival (OS) were analyzed by a Cox proportional hazards model. The results of the comparisons between the groups showed significant differences between the two groups in terms of age, body mass index, tumor site, Tumor-Node-Metastasis stage, initial treatment, hemoglobin level, GNRI and albumin level. The T10 sarcopenia group exhibited significantly lower PFS and OS rates compared with the T10 non-sarcopenia group at all time points. The 1- and 3-year PFS rates of the T10 sarcopenia group compared with those of the T10 non-sarcopenia group were 50.8 and 73.4%, and 15.3 and 37.5%, respectively. The median PFS times for the two groups were 12.0 and 24.7 months, respectively. The 1- and 3-year OS rates were 81.4 and 95.3%, and 25.4 and 64.1%, respectively. The median OS time was 22.1 months in the T10 sarcopenia groups and not reached in the T10 non-sarcopenia group. ROC curve analysis showed that T10 SMVI, PNI and GNRI all predicted the long-term survival of elderly patients with ESCC following radiotherapy, and that the predictive efficacy of T10 SMVI was higher than that of the hematological nutritional indicators PNI and GNRI, and was an independent influencing factor of OS. In conclusion, T10 SMVI can quantify the nutritional status of thoracic skeletal muscle and is more efficient than PNI and GNRI for predicting the prognosis of elderly patients with ESCC, providing a reference for clinical evaluation of skeletal muscle dystrophy. The present study pioneers the application of T10 SMVI derived from radiotherapy planning CT, offering a cost-effective, standardized method to assess skeletal muscle nutrition in elderly patients with ESCC.

Objective To investigate the correlation between quantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) after neoadjuvant chemotherapy and pathological grades in esophageal squamous cell carcinoma. Methods Fifty-six patients with esophageal squamous cell carcinoma who were confirmed by esophagoscope and received neoadjuvant chemotherapy before operation between September 2015 and December 2017 in the Affiliated Cancer Hospital of Zhengzhou University were prospectively analyzed,and MRI examination was performed within one week before operation. All patients underwent routine chest MRI and DCE-MRI scanning,and quantitative parameters of DCE-MRI,including volume transfer constant (Ktrans),exchange rate constant (Kep) and extravascular extracellular volume fraction (Ve) were measured. Pathological grading was assessed as highly differentiated,moderately differentiated,poorly differentiated,and undifferentiated. Intraclass correlation coefficient (ICC) was calculated from the results of two radiologists. Kruskal-Wallis H test was used to compare the differences of quantitative parameters between different pathological grade groups of DCE-MRI,and Mann-Whitney U test was utilized to compare the intraclass differences among pathological grades. Spearman rank correlation analysis was performed for evaluating the correlation between DCE-MRI parameters and pathological grade of esophageal squamous cell carcinoma. The receiver operating characteristic (ROC) curves were used to evaluate the diagnosis accuracy of different DCE-MRI parameters in pathological grade of esophageal squamous cell carcinoma after neoadjuvant chemotherapy. Results The 56 patients were divided into four groups according to pathological findings:well differentiated group (n=8),moderately differentiated group (n=39),poorly differentiated group (n=9) and undifferentiated group (n=0). The differences of Ktransmean,Ktrans75%,Kepmax,Kepmean,Kep75% between different pathological grading groups were statistically significant (all P<0.05),and these parameters showed positive correlation significantly with pathological grading (r values were 0.778, 0.632, 0.594, 0.725, 0.489 respectively,all P<0.05). The ROC curve area of Ktransmean,Ktrans75% in the diagnosis of pathological grade for esophageal squamous cell carcinoma was 0.750,0.856,respectively. The diagnostic efficiency of Ktrans75% was the best with the diagnostic threshold of 0.693/min,sensitivity of 87.5%,specificity of 78.5%,respectively. Conclusion The quantitative parameters of DCE-MRI after neoadjuvant chemotherapy in esophageal squamous cell carcinoma have the potential value for predicting pathological grade. Key words: Esophageal neoplasms; Magnetic resonance imaging; Pathology

Esophageal squamous cell carcinoma (ESCC) is a gastrointestinal carcinoma with a poor prognosis. To improve the survival of patients with this disease, neoadjuvant chemotherapy (NAC) has been introduced. However, the survival benefits of NAC or the correlation between NAC and postoperative complications have not been well considered. In the present study, we retrospectively investigated the clinicopathological effectiveness of NAC in patients with clinical stage II and III thoracic ESCC. This retrospective study enrolled 63 patients with clinical stage II and III thoracic ESCC, who underwent resection of the thoracic esophagus and three-field lymph node dissection between January 2007 and December 2013. NAC with cisplatin plus 5-fluorouracil (5-FU) was introduced in 38 patients. NAC did not correlate with the occurrence of postoperative complications. The 5-year disease-free survival (DFS) rate of the 38 patients with NAC (41.6%) was similar to that for the 25 patients who did not receive NAC (38.1%; P = 0.784). However, we found that the DFS of 17 patients with histopathological Grade 2 and 3 tumors who received NAC (5-year DFS rate: 58.1%) was significantly higher than that of 21 patients with low histopathological grade tumors who received NAC (5-year DFS rate: 28.6%), or than that of the 25 patients who did not receive NAC (38.1%). Moreover, we found that the effectiveness of NAC assessed macroscopically did not correlate with the effectiveness of NAC assessed microscopically. These findings may indicate that preoperative estimation of NAC effectiveness is important in avoiding unnecessary adverse drug effects caused by NAC, and in prolonging the survival of patients with thoracic ESCC. * Corresponding author.

e16124 Background: It has been proven that neoadjuvant therapy plays a vital part in the therapy of resectable esophageal squamous cell carcinoma (ESCC). Several studies have shown that adding immunotherapy to neoadjuvant chemo (-radiation) therapy can effectively improve R0 resection rate and even the prognosis. Toripalimab has been widely used in clinical practice of advanced staged carcinoma. Anti-angiogenesis therapy also plays an important role in treating advanced ESCC. Moreover, there have been a few of clinical studies attempting to add anti-angiogenesis therapy to neoadjuvant chemotherapy for ESCC, but no results reported so far. This study aims to explore the safety and efficacy of neoadjuvant chemotherapy combined with anti-angiogenesis therapy and immunotherapy for ESCC patients. Methods: This prospective, single-center, single-arm, phase 2 clinical trial recruits the treatment-naive patients with resectable ESCC. Twenty-five patients are planned to be enrolled in this study. Eligible patients are those with stage II to IIIB ESCC from cT2N1-2M0 to cT3N0-2M0, which have been pathologically diagnosed. They will receive Toripalimab 240mg plus Anlotinib 12mg (q.o.d. for two weeks) and chemotherapy (albumin-bound paclitaxel 200-260mg/m2 and Carboplatin 200-400mg/m2) every three weeks for four cycles. After the neoadjuvant therapy of 4-6weeks, patients will receive radical surgery for esophageal carcinoma. After surgery, Toripalimab will be administered for a year depending on patients’ will. The primary endpoint is the rate of pCR, and the secondary endpoints include ORR, DCR, DFS and OS. Results: In the first stage of the study, 4 patients achieved a pCR, allowing the trial to progress to the second phase. On the basis of Simon's Two-Stage design, 10 patients with stage II to IIIB ESCC from cT2N1-2M0 to cT3N0-2M0 were recruited for the first stage from the Nanfang Hospital, Southern Medical University from November 1, 2023, to June 25, 2024. The efficacy and safety analysis were evaluated in all patients (n = 10), 4 of the 10 patients achieved pCR (40%,) and 2 achieved mPR (20%). Evaluating by RECIST1.1 standard, the ORR was 90% (9/10, 95% CI, 59.59-98.21) and DCR was 100% (10/10, 95% CI, 72.25-100), while 5(50%) patients and 4 (40%) patients achieved a CR and PR respectively, and 1 (10%) patient got SD. The individual pathological results were not completely consistent with the imaging evaluation results. Among 10 patients in the first stage, 8 (80%) patients had treatment-related adverse events (TRAEs). More than 10% of incidence rate included paresthesia (n = 5), oral hemorrhage (n = 2), leukopenia (n = 2). G3-4 of TRAEs were dysphagia (n = 2). Conclusions: This neoadjuvant chemotherapy combined with anti-angiogenesis therapy and immunotherapy has exhibited notable efficacy and manageable safety profile in resectable ESCC. Clinical trial information: NCT05996484 .

The impact of anastomotic leak (AL) on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC) remains unclear. This study investigated whether AL influences the long-term survival of patients with ESCC following McKeown esophagectomy. An original database was queried to identify patients with ESCC who underwent McKeown esophagectomy between 2012 and 2020 at a high-volume cancer center. Overall survival (OS) and disease-free survival (DFS) were compared using Kaplan-Meier (KM) curves. Cox regression analysis was used for multivariate analysis. Propensity score matching (PSM) was used to adjust for the confounding factors. A total of 1614 patients were included, of whom 16.9% developed AL. In patients without neoadjuvant therapy, for patients with and without AL, the 5-year OS was 55.8% and 62.0%, and the 5-year DFS was 48.7% and 59.1%, respectively (OS: p = 0.37, DFS: p = 0.046). In the neoadjuvant cohort, for patients with and without AL, the 5-year OS was 57.9% and 63.2%, and the 5-year DFS was 55.4% and 58.8%, respectively (OS: p = 0.48, DFS: p = 0.78). Moreover, AL significantly increased the risk of distant recurrence in patients without neoadjuvant therapy (p = 0.023). These findings suggest that AL negatively influences DFS in patients without neoadjuvant therapy, but does not significantly affect long-term survival in patients receiving neoadjuvant treatment. Intensive treatment and follow-up plan should be considered when patients without neoadjuvant therapy.