Neoadjuvant chemotherapy combined with immunotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

BACKGROUND: To date, few studies have compared effectiveness and survival rates of neoadjuvant chemotherapy combined with immunotherapy (NACI) and conventional neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). The present study was conducted to compare therapeutic response and survival between NACI and NCRT. METHODS: The study cohort comprised patients with locally advanced ESCC treated with either NACI or NCRT followed by surgery between June 2018 and March 2021. The 2 groups were compared for treatment response, 3-year overall survival (OS), and disease-free survival (DFS). Survival curves were created using the Kaplan-Meier method, differences were compared using the log-rank test, and potential imbalances were corrected for using the inverse probability of treatment weighting (IPTW) method. RESULTS: Among 202 patients with locally advanced ESCC, 81 received NACI and 121 received conventional NCRT. After IPTW adjustment, the R0 resection rate (85.2% vs 92.3%; P = .227) and the pathologic complete response (pCR) rate (27.5% vs 36.4%; P = .239) were comparable between the 2 groups. Nevertheless, patients who received NACI exhibited both a better 3-year OS rate (91.7% vs 79.8%; P = .032) and a better 3-year DFS rate (87.4% vs 72.8%; P = .039) compared with NCRT recipients. CONCLUSIONS: NACI has R0 resection and pCR rates comparable to those of NCRT and seems to be correlated with better prognosis than NCRT. NACI followed by surgery may be an effective treatment strategy for locally advanced ESCC.

Pathologic responses and surgical outcomes after neoadjuvant immunochemotherapy versus neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Background: Currently, the role of immunotherapy in neoadjuvant setting for patients with locally advanced esophageal squamous cell carcinoma (ESCC) is gradually attracting attention. Few studies compared the efficacy of neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT). Our study aimed to compare treatment response and postoperative complications after NICT followed by surgery with that after conventional NCRT in patients with locally advanced ESCC. Methods: Of 468 patients with locally advanced ESCC, 154 received conventional NCRT, whereas 314 received NICT. Treatment response, postoperative complications and mortality between two groups were compared. Pathological response of primary tumor was evaluated using the Mandard tumor regression grade (TRG) scoring system. Pathological complete response (pCR) of metastatic lymph nodes (LNs) was defined as no viable tumor cell within all resected metastatic LNs. According to regression directionality, tumor regression pattern was summarized into four categories: type I, regression toward the lumen; type II, regression toward the invasive front; type III, concentric regression; and type IV, scattered regression. Inverse probability propensity score weighting was performed to minimize the influence of confounding factors. Results: After adjusting for baseline characteristics, the R0 resection rates (90.9% vs. 89.0%, P=0.302) and pCR (ypT0N0) rates (29.8% vs. 34.0%, P=0.167) were comparable between two groups. Patients receiving NCRT showed lower TRG score (P<0.001) and higher major pathological response (MPR) rate (64.7% vs. 53.6%, P=0.001) compared to those receiving NICT. However, NICT brought a higher pCR rate of metastatic LNs than conventional NCRT (53.9% vs. 37.1%, P<0.001). The rates of type I/II/III/IV regression patterns were 44.6%, 6.8%, 11.4% and 37.1% in the NICT group, 16.9%, 8.2%, 18.3% and 56.6% in the NCRT group, indicating a significant difference (P<0.001). Moreover, there were no significant differences in the incidence of total postoperative complications (35.8% vs. 39.9%, P=0.189) and 30-d mortality (0.0% vs. 1.1%, P=0.062). Conclusion: For patients with locally advanced ESCC, NICT showed a R0 resection rate and pCR (ypT0N0) rate comparable to conventional NCRT, without increased incidence of postoperative complications and mortality. Notablely, NICT followed by surgery might bring a promising treatment response of metastatic LNs.

Development and validation of a nomogram model for the prediction of 4L lymph node metastasis in thoracic esophageal squamous cell carcinoma.

Objectives: The left tracheobronchial (4L) lymph nodes (LNs) are considered as regional LNs for esophageal squamous cell carcinoma (ESCC), but there is a controversy about routine prophylactic 4L LN dissection for all resectable ESCCs. This study aimed to develop a nomogram for preoperative prediction of station 4L lymph node metastases (LNMs). Methods: A total of 522 EC patients in the training cohort and 370 in the external validation cohort were included. The prognostic impact of station 4L LNM was evaluated, and multivariable logistic regression analyses were performed to identify independent risk factors of station 4L LNM. A nomogram model was developed based on multivariable logistic regression analysis. Model performance was evaluated in both cohorts in terms of calibration, discrimination, and clinical usefulness. Results: The incidence of station 4L LNM was 7.9% (41/522) in the training cohort. Patients with station 4L LNM exhibited a poorer 5-year overall survival rate than those without (43.2% vs. 71.6%, p < 0.001). In multivariate logistic regression analyses, six variables were confirmed as independent 4L LNM risk factors: sex (p = 0.039), depth of invasion (p = 0.002), tumor differentiation (p = 0.016), short axis of the largest 4L LNs (p = 0.001), 4L conglomeration (p = 0.006), and 4L necrosis (p = 0.002). A nomogram model, containing six independent risk factors, demonstrated a good performance, with the area under the curve (AUC) of 0.921 (95% CI: 0.878-0.964) in the training cohort and 0.892 (95% CI: 0.830-0.954) in the validation cohort. The calibration curve showed a good agreement on the presence of station 4L LNM between the risk estimation according to the model and histopathologic results on surgical specimens. The Hosmer-Lemeshow test demonstrated a non-significant statistic (p = 0.691 and 0.897) in the training and validation cohorts, which indicated no departure from the perfect fit. Decision curve analysis indicated that the model had better diagnostic power for 4L LNM than the traditional LN size criteria. Conclusions: This model integrated the available clinical and radiological risk factors, facilitating in the precise prediction of 4L LNM in patients with ESCC and aiding in personalized therapeutic decision-making regarding the need for routine prophylactic 4L lymphadenectomy.

99m Tc bone scintigraphy does not affect preoperative workup for patients with potentially resectable esophageal squamous cell carcinoma.

BACKGROUND: 99m Tc bone scintigraphy (BS) is the mainstay and most widely used technique in evaluation of bone metastasis (BM) in China. This study aimed to investigate the value of 99m Tc BS in preoperative workup for patients with potentially resectable (cT1-4a N0-3 ) esophageal squamous cell carcinoma (ESCC). METHODS: This prospective cross-section clinical trial (ChiCTR1800020304) enrolled a total of 385 patients with ESCC diagnosed at thoracic surgery clinic from October 2018 to September 2020. All patients were diagnosed with stage cT1-4a N0-3 and were potential candidates for surgical resection. BS was performed preoperatively and the treatment strategy was changed after confirmation of BM. The primary endpoint was the rate of change of the treatment regimen because of BM, while the secondary endpoint was the rate of positive BS findings. RESULTS: Out of the 385 patients, only two (0.5%) changed their treatment regimen because of BM. The rate of positive BS findings was 1%, while two patients (0.5%) had false-positive or false-negative results. The BS diagnostic performance for BM was sensitivity 50%, specificity 99.5%, positive predictive value 50%, negative predictive value 99.5%, and accuracy 99.0%. There was no significant difference in BM in relation to age, sex, tumor location or clinical stage. CONCLUSION: Our data demonstrated that 99m Tc bone scintigraphy does not significantly affect the preoperative workup in patients with potentially resectable ESCC, especially in early clinical stage patients.

Clinical significance of left tracheobronchial lymph node dissection in thoracic esophageal squamous cell carcinoma.

OBJECTIVE: The left tracheobronchial lymph nodes are considered as regional lymph nodes for esophageal squamous cell carcinoma, but routine prophylactic left tracheobronchial lymph node dissection for all resectable esophageal squamous cell carcinoma has been controversial. This study aimed to evaluate the prognostic impact of left tracheobronchial lymph node dissection and left tracheobronchial lymph node metastases in thoracic esophageal squamous cell carcinoma and to analyze the risk factors of left tracheobronchial lymph node metastases. METHODS: A total of 3522 patients with esophageal squamous cell carcinoma undergoing esophagectomy were included. Overall survival was calculated by a Kaplan-Meier method and compared using the log-rank test. Propensity score matching was conducted to adjust confounding factors. Univariable and multivariable logistic regression analyses were used to identify independent risk factors of left tracheobronchial lymph node metastases. RESULTS: In this study, 608 patients underwent left tracheobronchial lymph node dissection and 45 patients had left tracheobronchial lymph node metastases (7.4%). After propensity score matching, the 5-year overall survival in patients receiving left tracheobronchial lymph node dissection was better than in patients who did not (68.2% vs 64.6%, P = .012). In patients receiving left tracheobronchial lymph node dissection, patients with left tracheobronchial lymph node metastases had a significantly poorer survival than patients without (5-year overall survival: 40.5% vs 62.2%, P = .029). Multivariable logistic analyses showed that clinical T stage and tumor differentiation were independent risk factors for left tracheobronchial lymph node metastases. CONCLUSIONS: In thoracic esophageal squamous cell carcinoma, station left tracheobronchial lymph node metastases indicate a poor prognosis and left tracheobronchial lymph nodes dissection seems to be associated with a more favorable prognosis. Clinical T stage and tumor differentiation were independent risk factors for left tracheobronchial lymph node metastases. For patients with high risk, routine prophylactic left tracheobronchial lymph node dissection should be performed.

Reconstruction of upper mediastinal pleura reduces postoperative complications in enhanced recovery surgery system after esophagectomy: A propensity score matching study.

OBJECTIVES: This study aimed to explore the effect of suturing upper mediastinum pleura on postoperative complications, surgery-related mortality, and hospital stay. METHODS: Four hundred and thirty-eight patients with esophageal cancer who underwent esophagectomy were identified. Patients were divided into two groups: those in the test group who received reconstruction of upper mediastinal pleura, those in the conventional group who did not. The incidence of postoperative complications, surgery-related mortality, and hospital stay were compared. To reduce the impact of confounding factors, a propensity score matching (PSM) method was performed. RESULTS: A total of 273 patients were treated with suturing upper mediastinal pleura and 165 were not. After PSM, compared with the conventional group, the incidence of atelectasis (7.2% vs. 1.4%, p = 0.035), anastomotic leakage (5.8% vs. 0.7%, p = 0.036), and delayed gastric emptying (10.8% vs. 3.6%, p = 0.034) were significantly lower in the test group. And suturing the upper mediastinal pleura could reduce the severity of leakage (p = 0.045), consistent with the results before PSM. Moreover, there were no significant differences in the incidence of other complications, postoperative hospital stay, and 30-day mortality (all p > 0.05). CONCLUSIONS: In this study, suturing the upper mediastinal pleura can reduce the incidence of atelectasis, anastomotic leakage, and delayed gastric emptying, and the severity of leakage, without increasing the incidence of other complications, surgery-related death, and postoperative hospital stay.

Treatment and Prognosis of Resectable Cervical Esophageal Cancer: A Population-Based Study.

BACKGROUND: The optimal treatment strategy for resectable cervical esophageal cancer remains controversial. This study aimed to explore prognostic factors and optimal treatment strategies in the context of staging. METHODS: In this population-based study, 1371 patients with resectable cervical esophageal cancer were identified in the Surveillance, Epidemiology, and End Results database. Univariate analysis and multivariable Cox regression model were performed to evaluate factors related to overall survival (OS). Subgroup analysis based on staging was performed to assess the effect of treatments on survival and propensity score matching was conducted to adjust confounding factors. RESULTS: Univariate and multivariable analyses revealed that age, sex, year of diagnosis, histological type, tumor size, cN stage, surgery, radiotherapy, and chemotherapy are independent prognostic factors. After propensity score matching, patients with local disease (cT1-2N0M0) who received surgery alone had a higher 10-year OS rate than those received chemoradiotherapy (CRT) (20.7% vs 11.4%, P = .023). Compared with CRT, surgery-based multimodal therapy did not increase the OS rate of patients (14.8% vs 11.1%, P = .084). For regional disease (cT3-4aN0M0/cT1-4aN1-3M0), although surgery alone did not improve the OS rate of patients compared with CRT (7.3% vs 8.2%, P = .18), we observed a significant difference in 10-year OS among patients who underwent surgery-based multimodal therapy vs those who underwent CRT (20.4% vs 9.0%, P = .031). CONCLUSIONS: Compared with CRT, surgery alone improves the long-term survival of patients with localized disease, and surgery-based multimodal therapy increases the survival rate of patients with regional disease. Further studies are required to confirm our findings.

Patient prognostic scores and association with survival improvement offered by postoperative radiotherapy for resected IIIA/N2 non-small cell lung cancer: A population-based study.

BACKGROUND: Currently, there is no consensus on the role of postoperative adjuvant radiotherapy (PORT) for resected stage IIIA/N2 non-small cell lung cancer (NSCLC). Our study sought to determine which patients may be able to benefit from PORT, based on a patient prognostic score. METHODS: A retrospective cohort study was conducted to identify patients diagnosed with IIIA/N2 NSCLC between 1988 and 2016 in the SEER database. Eligible patients were divided into the following two groups: PORT group and non-PORT group. We classified patient prognostic scores as an ordinal factor and stratified patients based on prognostic scores. A Cox proportional hazards model with propensity score weighting was performed to evaluate cancer-specific mortality (CSM) between the two groups. RESULTS: We identified 7060 eligible patients with IIIA/N2 NSCLC, 2833 (40.1%) in the PORT group and 4227 (59.9%) in the non-PORT group. Overall, the 10-year CSM rate in the weighted cohorts was 70.4% in the PORT group, 72.0% in the non-PORT group, and patients who received PORT had a lower CSM rate (p = 0.001). Compared with the non-PORT group, significant survival improvements in the PORT group were observed in patients with higher age, grade, T stage and lymph node ratio (LNR), and without chemotherapy. The improved survival of patients receiving PORT was significantly correlated with patient prognostic scores (p < 0.001). CONCLUSIONS: In our population-based study, the prognostic score was associated with the survival improvement offered by PORT in IIIA/N2 NSCLC, suggesting that prognostic scores and clinicopathological characteristics may be helpful in proper candidate selection for PORT.