Surgery For Esophageal Carcinoma Research Articles

1464P Chemo-radiation alone associated with higher risk of death compared to chemo-radiation plus surgery in esophageal squamous cell carcinoma

1464P Chemo-radiation alone associated with higher risk of death compared to chemo-radiation plus surgery in esophageal squamous cell carcinoma

332. OUTCOMES OF SALVAGE SURGERY FOR ESOPHAGEAL CARCINOMA: A NATIONWIDE COHORT STUDY

Abstract Background Compared to a standard resection, salvage esophagectomy is a more complex procedure and associated with increased postoperative morbidity and mortality. This study aimed to investigate short-term outcomes of salvage surgery for esophageal carcinoma and the influence of hospital volume and baseline characteristics on outcomes. Methods All patients undergoing esophagectomy for esophageal cancer registered in the Dutch Upper Gastrointestinal Cancer Audit (DUCA) between 2012-2022 in the Netherlands were included. Patients were classified as salvage or non-salvage by registering surgeons. The definition was: surgery after definitive chemoradiotherapy. Postoperative mortality (30-day/-in-hospital) and morbidity were compared between salvage and non-salvage patients using multilevel logistic regression analyses. Hospital variation in the use of salvage esophagectomy was investigated using funnel plots. The influence of annual hospital volume (<40->40) and annual salvage volume (<6->6) on outcomes of salvage patients were investigated. Using backward elimination, relevant baseline characteristics influencing outcomes after salvage surgery were identified. Results Between 2012-2022, 7,749 patients underwent esophagectomy, of whom 251 (3%) underwent salvage resection, varying from 0%-8% of esophagectomies between centers. Salvage surgery was associated with an increased risk of 30-day/in-hospital mortality (11% vs. 3%; OR:3.65; 95%CI:2.38-5.61) and severe complications (43% vs. 28%; OR:1.81; 95%CI:1.40-2.34). Salvage patients treated in high-volume esophagectomy centers (>40) had a decreased risk of 30-day/in-hospital mortality compared to low-volume centers (9% vs. 19%; OR:0.42; 95%CI:0.18-0.99), with no relation found between annual salvage volume and outcome. Certain baseline characteristics, foremost men, elderly (>75 years) and squamous cell carcinomas, were associated with worse short-term outcomes of salvage surgery. Conclusion Salvage surgery for esophageal carcinoma is infrequently but increasingly performed in the Netherlands, with wide hospital variation in its use. Salvage surgery is associated with worse short-term outcomes when compared with non-salvage esophagectomy. Outcomes after salvage surgery were favorable in high-volume esophagectomy centers, suggesting a volume-outcome relationship for salvage surgery.

Esophagectomy in patients with esophageal squamous cell carcinoma and distant nodal metastasis.

The role of surgery in oligometastatic esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the oncological outcomes after esophagectomy in patients with ESCC with distant lymph node (LN) metastasis. Patients with ESCC and nodal metastasis treated with chemoradiotherapy or chemotherapy followed by esophagectomy between 2010 and 2020 were included. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients with distant LN metastasis (dLN+) and exclusively regional LN metastasis (dLN-). The cohort comprised 69 dLN+ and 111 dLN- patients. Survival was significantly better in the dLN- group than in the dLN+ group (5-year OS, 51.9% vs. 25.5%, P < 0.001; RFS, 47.2% vs. 18.1%, P < 0.001). Stratified by the yp stage, 49 (44.1%) dLN- and 30 (43.5%) dLN+ patients achieved a pathological complete response (pCR). In the dLN- and dLN+ groups, the OS rates were significantly higher in the pCR group than in the non-pCR group (dLN-: 76.7% vs. 32.4%, P < 0.001; dLN+: 39.6% vs. 14.2%; P = 0.002). The dLN-/pCR group had the best OS, significantly outperforming the dLN-/non-pCR and dLN+/pCR groups. OS did not differ between the dLN-/non-pCR and dLN+/pCR groups. The dLN+/non-pCR group had the worst OS. The RFS analysis paralleled the OS findings. Patients with dLN+ disease had worse outcomes than their dLN- counterparts, irrespective of the pCR status. The survival rates were poor but comparable between the dLN+/pCR and dLN-/non-pCR groups. Adjuvant therapy may be required for dLN+ patients following systemic treatment and surgery, even after achieving pCR.

Multicentre randomized clinical trial on robot-assisted versus video-assisted thoracoscopic oesophagectomy (REVATE trial).

Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).

Development and Validation Study of the Prognostic Impact of Deep Learning-Determined Myxoid Stroma After Neoadjuvant Chemotherapy in Patients with Esophageal Squamous Cell Carcinoma.

This study was designed to investigate the prognostic significance of artificial intelligence (AI)-based quantification of myxoid stroma in patients undergoing esophageal squamous cell carcinoma (ESCC) surgery after neoadjuvant chemotherapy (NAC) and to verify its significance in an independent validation cohort from another hospital. We evaluated two datasets of patients with pathological stage II or III ESCC who underwent surgery after NAC. Cohort 1 consisted of 85 patients who underwent R0 surgery for the primary tumor after NAC. Cohort 2, the validation cohort, consisted of 80 patients who received same treatments in another hospital. AI-based myxoid stroma was evaluated in resected specimens, and its area was categorized by using the receiver operating characteristic curve for overall survival (OS) of cohort 1. The F1 scores, which are the degree of agreement between the automatically detected myxoid stroma and manual annotations, were 0.83 and 0.79 for cohorts 1 and 2. The myxoid stroma-high group had a significantly poorer prognosis than the myxoid stroma-low group in terms of OS, disease-specific survival (DSS), and recurrence-free survival (RFS) in cohort 1. Comparable results were observed in cohort 2, where OS, DSS, and RFS were significantly affected by myxoid stroma. Multivariate analysis for RFS revealed that AI-determined myxoid stroma-high was one of the independent prognostic factors in cohort 1 (hazard ratio [HR] 1.97, p = 0.037) and cohort 2 (HR 4.45, p < 0.001). AI-determined myxoid stroma may be a novel and useful prognostic factor for patients with pathological stage II or III ESCC after NAC.

Efficiency of conversion surgery for esophageal squamous cell carcinoma with solitary abdominal para-aortic lymph node metastasis.

Abdominal para-aortic lymph nodes (PANs) are sites of distant metastasis in esophageal squamous cell cancer (ESCC). The prognosis of patients with Stage IVB ESCC and abdominal PAN metastasis is extremely poor. However, chemotherapy for ESCC has recently been developed, and the effectiveness of combined induction therapy and conversion surgery remains unclear. The primary objective of this study was to evaluate the short- and long-term outcomes of conversion surgery for ESCC and solitary abdominal PAN metastases after induction therapy. Thirteen patients who underwent conversion esophagectomy for cStage IVB ESCC with solitary abdominal PAN metastasis after induction therapy between January 2017 and October 2022 at our institution were enrolled. The short- and long-term outcomes of conversion surgery were retrospectively evaluated. Three patients (23.1%) had pathological abdominal PAN metastasis, and six patients (46.2%) without pathological abdominal PAN metastasis showed that chemotherapy eliminated the tumors in the abdominal PAN. Three patients (23.1%) had postoperative complications of Clavien-Dindo grade II or higher. The 3-year overall and recurrence-free survival rates were 83.1% and 51.3%, respectively. Our findings showed that conversion surgery for ESCC and solitary abdominal PAN metastasis led to a good prognosis when induction therapy was successful.

Endoscopic submucosal dissection versus surgery for T1b esophageal carcinoma: a single-center retrospective study

IntroductionEndoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery, especially for T1b SESCC. This study compared the overall survival (OS), disease-free survival (DSS), recurrence-free survival (RFS), and complication rates of both, to evaluate the value of ESD in patients with T1b SESCC.MethodsWe reviewed patients who underwent ESD (n = 47) or surgery (n = 73) for T1b SESCC at Affiliated Hospital of Nanjing University of Chinese Medicine from 2009 to 2021. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion and elderly people.ResultsIn the ESD and surgery groups, the overall mortality rates were 0/100 and 12.3/100 person years, incidence rates of recurrence were 2.13/100 and 11/100 person years, respectively. Kaplan–Meier survival analysis revealed no significant different in OS, DSS and RFS. Charlson comorbidity index (CCI) and depth of submucosal invasion were identified as risk factors for cancer recurrence in multivariate analysis. For elderly people, no significant differences were found in OS, DSS and RFS between different treatments.ConclusionESD are related to lower complication rates and shorter hospital stay than surgery in long-term outcomes for patients with pT1b SESCC. But in pT1b-SM2 patients, we still need long-term follow-up.

Recurrence-free survival as a surrogate endpoint for overall survival after neoadjuvant chemotherapy and surgery for oesophageal squamous cell carcinoma.

Overall survival is considered as one of the most important endpoints of treatment efficacy but often requires long follow-up. This study aimed to determine the validity of recurrence-free survival as a surrogate endpoint for overall survival in patients with surgically resectable advanced oesophageal squamous cell carcinoma (OSCC). Patients with OSCC who received neoadjuvant cisplatin and 5-fluorouracil, or docetaxel, cisplatin and 5-fluorouracil, at 58 Japanese oesophageal centres certified by the Japan Esophageal Society were reviewed retrospectively. The correlation between recurrence-free and overall survival was assessed using Kendall's τ. The study included 3154 patients. The 5-year overall and recurrence-free survival rates were 56.6 and 47.7% respectively. The primary analysis revealed a strong correlation between recurrence-free and overall survival (Kendall's τ 0.797, 95% c.i. 0.782 to 0.812) at the individual level. Subgroup analysis showed a positive relationship between a more favourable pathological response to neoadjuvant chemotherapy and a higher τ value. In the meta-regression model, the adjusted R2 value at the institutional level was 100 (95% c.i. 40.2 to 100)%. The surrogate threshold effect was 0.703. There was a strong correlation between recurrence-free and overall survival in patients with surgically resectable OSCC who underwent neoadjuvant chemotherapy, and this was more pronounced in patients with a better response to neoadjuvant chemotherapy.

Prognosis of patients with residual pathological disease after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy and surgery for esophageal squamous cell carcinoma: a retrospective cohort study.

Docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy has been established as one of the standard neoadjuvant therapies for locally advanced esophageal squamous cell carcinoma (ESCC). However, little is known about prognostic factors in patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC who are candidates for adjuvant nivolumab. This study aimed to investigate prognostic factors in patients with residual pathological disease after neoadjuvant DCF chemotherapy followed by surgery for locally advanced ESCC. This was a retrospective cohort study. This retrospective cohort study included patients who received neoadjuvant DCF followed by surgery for locally advanced ESCC between June 2014 and January 2020 at the National Cancer Center Hospital East. Among a total of 210 patients, 45 patients (21.4%) achieved a pathological complete response. The 3-year disease-free survival (DFS) rate was significantly lower in patients with residual pathological disease than in those with a pathological complete response [53.5% versus 74.5%; hazard ratio (HR): 2.09, 95% confidence interval (CI): 1.16-3.77, p = 0.01]. In patients with residual pathological disease (n = 165), multivariate analysis revealed that pathological node positivity (HR: 3.59, 95% CI: 1.92-6.71, p < 0.01), supraclavicular lymph node metastasis (HR: 2.15, 95% CI: 1.19-3.90, p = 0.01), and lymphovascular invasion (HR: 1.90, 95% CI: 1.14-3.17, p = 0.02) were significantly associated with poor DFS. In this largest-to-date cohort study, patients with residual pathological disease after neoadjuvant DCF followed by surgery for locally advanced ESCC had a poor prognosis. In these patients, pathological node positivity, including supraclavicular lymph node metastasis, and lymphovascular invasion were considered significant prognostic factors.

Prognostic role of pathologic status other than complete response after neoadjuvant therapy followed by surgery in esophageal squamous cell carcinoma.

This retrospective study was performed to investigate the survival differences according to the pathologic status after neoadjuvant chemotherapy followed by surgery in esophageal squamous cell carcinoma (ESCC), and to investigate whether current AJCC 8th ypStage can predict survival accurately. Data of 563 patients who received neoadjuvant therapy and esophagectomy for ESCC between 1994 and 2018 were retrospectively reviewed. The mean age was 62.00 ± 8.01years, of which 524 (93.1%) were males. The median follow-up period was 29.12months. A total of 153 (27.1%) patients showed pathologic complete response (pCR) and 92 (16.3%) patients showed pCR of the primary lesion with residual metastatic lymph nodes (ypT0N +). A total of 196 (35%) and 122 (21.6%) patients showed ypT + N + and ypT + N, respectively. The 5-year overall survival (OS) of each group was 75.1% (CR), 42.4% (ypT + N0), 54.9% (ypT0N +), and 26.1% (ypT + N +); CR patients showed better survival than the other groups, and no survival differences were found in the 5-year OS between ypT + N0 and ypT0N + patients (p = 0.811). In ypStage I, there were survival differences between ypT0N0 and ypTis-2N0 patients, and ypT1N0 (ypStage I) and ypT0N1 (ypStageIIIA) showed similar OS (5-year OS in 49.3% vs. 67.1%, p = 0.623). pCR offers long-term survival in patients; however, survival significantly declines with the presence of residual primary lesion and nodal metastases.

Comparison of central venous catheter thoracic drainage and traditional closed thoracic drainage following minimally invasive surgery for esophageal carcinoma: a retrospective analysis

ObjectiveTo compare the effectiveness and safety of central venous catheter thoracic drainage (CVCTD) with traditional closed thoracic drainage (TCTD) after minimally invasive surgery for esophageal cancer.MethodsWe conducted a retrospective investigation of 103 patients who underwent minimally invasive esophageal cancer surgery at our institution between January 2017 and December 2019. Among them, 44 patients underwent CVCTD, while 59 received TCTD. We compared the following outcomes between the two cohorts: drainage volume, duration of drainage, postoperative complications (including pleural effusion, pulmonary infection, atelectasis, anastomotic leakage, etc.), length of hospital stay, and postoperative pain assessment.ResultsNo significant differences were observed between the experimental and control groups regarding postoperative thoracic drainage, the timing of postoperative tube removal, or postoperative complications. However, significant disparities were noted in the duration of postoperative hospitalization, drainage tube healing time, and pain threshold among the esophageal cancer patients in both cohorts (p < 0.05).ConclusionCVCTD is a secure and potent alternative to TCTD following minimally invasive surgery for esophageal carcinoma. It potentially contributes to reducing the incidence of postoperative complications while curtailing the duration of hospitalization. Additional research is warranted to substantiate these findings.

The relationship between preoperative anemia and length of hospital stay among patients undergoing radical surgery for esophageal carcinoma: a single-centre retrospective study

BackgroundAlthough it is unclear if preoperative anemia affects patients undergoing radical resection of esophageal cancer, it does increase the length of stay (LOS) for surgical patients. Accordingly, the purpose of this study was to investigate if, after adjusting for other covariates, anemia was independently associated with LOS in people undergoing radical resection of esophageal cancer.MethodsThe retrospective cohort study included 680 patients undergoing radical esophageal cancer surgery between January 2010 and December 2020. Preoperative anemia was the targeted independent variable, while LOS was the target independent variable. Demographics, comorbidities, laboratory tests, surgery and anesthesia, postoperative outcomes, and complications were collected. Multivariate linear analyses were performed for variables that might influence preoperative anemia and LOS selection. Subgroup analysis using hierarchical variables was then used to test the potential relationship.ResultsThe 647 individuals that were randomly chosen had an average age of 61.06 ± 8.16 years, and 77.43% of them were male. The prevalence of anemia was 36.6%. All patients recruited had an average length of stay (LOS) of 26.31 ± 13.19 days, 25.40 ± 11.44 days for patients who had no preoperative anemia, and 27.89 ± 15.66 days for patients who had preoperative anemia, p < 0.05. After adjusting for covariates, the results of fully adjusted linear regression revealed that preoperative anemia was significantly associated with LOS (β = 2.04, 95%CI (0.13, 3.96) ), p < 0.05. The results of the subgroup analysis were basically accurate and steady. Regardless of gender, same outcomes were seen when preoperative anemia was defined as a Hb level < 13 g/dL (β = 2.29, 95%CI (0.33, 4.25) ), p < 0.05. In addition, the LOS was shortened with the increase of preoperative hemoglobin (Hb) (β= -0.81, 95%CI (-1.46, -0.1) ), p < 0.05.ConclusionPreoperative anemia is typical in Chinese patients undergoing radical esophageal cancer resection and is independently associated with prolonged LOS.

Long-Term Outcomes in a Phase II Study of Hypofractionated IGRT 60Gy/ 20F in Patients with Isolated Lymph Node Recurrence after Surgery for Esophageal Carcinoma

In oligo metastases in lymph node recurrence after surgery for esophageal cancer, since SBRT (BED>100 Gy10) to mediastinal and abdominal lymph node lesions was not an option due to toxicities in the organs at risk (OAR) such as vessels and gastrointestinal tract, we performed a prospective cohort study of hypofractionated IGRT for isolated lesions. The primary end-points of this study are disease specific survival (DSS) and late treatment toxicities. From 2011 to 2021, 60 Gy/20F/4-4.5wks (78 Gy10) hypofractionated IGRT was performed in a total ITT population of 70 patients after radical surgery (67 cases) and ESD (3 cases), who were diagnosed by CT/PET-CT as having solitary lymph node recurrence (62 cases) or up to 2 adjacent nodes (8 cases). The mean time from surgery to recurrence was 17.9 months (SD 18.1) with a mean age of 67.5 years (SD 9.3), and male to female ratio was 62:8. Pathological results showed that 63 patients (90%) had squamous cell carcinoma. The mean maximum diameter of lesions was 2.5 cm (SD; 1.1 cm). And 51 cases (73%) were treated with CRT concurrently using 5FU plus CDDP (FP), and the rest were treated with RT alone. Lymph node location was lower neck or upper mediastinum in 42 cases, middle and lower mediastinum in 16 cases, and abdomen in 12 cases, respectively. Treatment planning was performed by taking 4DCT fusing PET or MRI images. The Kaplan-Meier method and the Cox proportional hazards regression model were used for overall survival (OS), DSS, and progression free survival (PFS). The mean observation period was 38 months. Primary efficacy was CR in 45 cases (64%), but CR was maintained only in 29 cases (41%). Twenty-two of the 70 patients were relapse-free. OS were 53% and 34% at 2 and 5 years, DSS were 56% and 38% at 2 and 5 years, and PFS were 40% and 39% at 2 and 5 years, respectively. The site of first recurrence was the same or adjacent lymph nodes in 33 cases (47%) and distant metastases in 9 cases (13%). Number of tumors (1 vs. 2), age, and CRT were not significant prognostic factors for OS, DSS, or PFS. In a multivariate analysis, the time from surgery to recurrence ≥12 months was the only significant prognostic factor for PFS (p = 0.018, HR0.50). The same multivariate analysis showed that the only significant prognostic factor for DSS was the location of the recurrent lymph node in the neck and upper mediastinal regions (p = 0.009, HR 0.59). The only late adverse events of Grade 2 or higher were Grade 2 pleural effusion (little and transient) in 6 cases and Grade 2 radiation pneumonitis in 1 case. No acute adverse events were observed other than hematologic toxicity due to FP administration. In locally advanced esophageal cancer, a relatively reliable regional lymph node dissection is often performed, so there is still a chance to aim for cure in cases of solitary recurrence. We found that if the lesion is solitary, localized RT of about 60 Gy/20F/4-4.5 weeks with IGRT can achieve a long-term survival in 40% of patients without any significant adverse events.

Effect of Histopathological Regression of Tumor and Lymph Node on the Progression of Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy

To investigate the regression of tumor and lymph node after neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC) and their impact on progression-free survival (PFS). We enrolled 181 patients with localized esophageal cancers (cT2-4, Nx, M0) who underwent neoadjuvant radiochemotherapy followed by surgery for esophageal carcinoma (EC) between March 2016 and December 2021. Patients clinical factors including age, gender, tumor location, cT stage, cN stage, cTNM stage, chemotherapy regimen, total radiation dose were collected. The pathologist evaluated the response of tumors and lymph nodes removed during esophagectomy, including ypT stage, ypN stage, complete pathological response (PCR) status, and tumor regression grading (TRG) stage. The Kaplan-Meier method was used for univariate analyses of PFS. Multivariate analysis of prognostic variables that showed significant association were further assessed by Cox proportional hazard model. The median PFS was 6.6 months. The primary tumors of 134 (74%) patients had pathological remission. The metastatic lymph node of 100 (55.2%) patients had pathological remission. Complete pathological remission was observed in 93(48.7%) patients. Univariate survival analysis identified cT stage (P:0.027), pT (P:0.001), pN (P:0.0001), TRG stage (P:0.0001), PCR status (P:0.001) as significant prognostic factors. Cox regression analysis identified dichotomized ypN (P:0.028) and TRG stage (P:0.034) as significant independent prognostic parameters. ypN and TRG stage were significant prognostic parameters for PFS in patients with neoadjuvant chemoradiotherapy for ESCC.

Long-term survival and prognostic factors associated with curative conversion surgery for ct4b esophageal squamous cell carcinoma: Analysis of 200 consecutive cases

BackgroundThe optimal treatment strategy for cT4b esophageal cancer has not been established yet. Although curative surgery is sometimes performed after induction treatments, the prognostic factor of cT4b esophageal cancer cases who underwent R0 resection remains unknown. MethodsA total of 200 patients with cT4b esophageal cancer who underwent R0 resection after induction treatments between 2001 and 2020 in our institute were included in the present study. The relationship between clinicopathological factors and patient survival is evaluated to identify useful prognostic factors. ResultsThe median and 2-year overall survival were 40.1 months and 62.8%, respectively. Disease recurrence occurred in 98 (49%) patients after surgery. Compared to induction chemotherapy alone, chemoradiation-based induction treatments were associated with decreased locoregional recurrence (34.0% vs 60.8%, P = .0077) but increased pulmonary metastases (27.7% vs 9.8%, P = .0210) and dissemination (19.1% vs 3.9%, P = .0139) after surgery. Multivariate analysis of overall survival identified the preoperative C-reactive protein/albumin ratio (hazard ratio 1.7957, P = .0031), response to induction treatments (hazard ratio 2.9663, P = .0009), postoperative pneumonia (hazard ratio 2.3784, P = .0010), and pN (2–3) (hazard ratio 1.5693, P = .0355) as independent prognostic factors. Preoperative C-reactive protein/albumin ratio (hazard ratio 1.6760, P = .0068) and postoperative pneumonia (hazard ratio 1.8365, P = .0200) were also independent prognostic factors for recurrence-free survival. ConclusionCurative surgery after induction therapy for cT4b esophageal cancer achieved favorable survival. Preoperative C-reactive protein/albumin ratio, postoperative pneumonia, response to induction treatments, and pN were useful prognostic factors.

ASO Visual Abstract: Patterns and Influence of Lymph Nodal Metastases After Neoadjuvant Chemotherapy and Surgery for Thoracic Esophageal Squamous Cell Carcinoma.

ASO Visual Abstract: Patterns and Influence of Lymph Nodal Metastases After Neoadjuvant Chemotherapy and Surgery for Thoracic Esophageal Squamous Cell Carcinoma.

Neoadjuvant Chemotherapy or Neoadjuvant Chemoradiotherapy for Patients with Esophageal Squamous Cell Carcinoma: Real-World Data Comparison from A Japanese Nationwide Study.

Although neoadjuvant treatment has become the standard of care for patients with locally advanced esophageal cancer, previous studies comparing neoadjuvant chemotherapy (NAC) and neoadjuvant chemoradiotherapy (NACRT) have demonstrated inconclusive results. Our study cohort included 3978 patients from 85 institutions. Those who underwent NAC or NACRT followed by surgery for esophageal squamous cell carcinoma (ESCC) were eligible for inclusion. We used the inverse probability of treatment weighting (IPTW) method to compare the outcomes between NAC and NACRT. Among the 3978 patients, 3777 (94.9%) received NAC and 201 (5.1%) received NACRT. After IPTW adjustment, the NACRT group had more patients with pathologically downstaged diseases and significantly better pathological response compared with the NAC group (p<0.001); however, 5-year overall survival (OS), recurrence-free survival (RFS), and regional recurrence-specific survival (RRSS) were comparable between the groups. Subgroup analysis stratifying patients according to cT category showed that among cT1-2 patients, those in the NACRT group had significantly longer 5-year OS, RFS, and RRSS than those in the NAC group (P = 0.024, < 0.001, and 0.020, respectively). In contrast, no significant differences were observed among cT3-4a patients. The competing risks regression model showed comparable subdistribution hazard ratios for 10-year cancerous and noncancerous deaths between the NAC and NACRT groups. Compared with NAC, NACRT for ESCC did not promote better survival despite better therapeutic effects and did not increase noncancerous deaths.

Patterns and Influence of Lymph Nodal Metastases After Neoadjuvant Chemotherapy and Surgery for Thoracic Esophageal Squamous Cell Carcinoma.

The purpose of this retrospective study was to define the pattern of lymph nodal metastases in patients with esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemotherapy (NCT) followed by esophagectomy and to evaluate its influenceonprognosis. A total of 398 patients with clinical stage T3N0 or T1-3N+ ESCC who underwent NCT and radical esophagectomy with two-field lymphadenectomy were included. The distribution and frequency of metastases were counted separately for each lymph node station. The ypN stage, number of positive lymph node stations and lymph node stations with a metastasis rate greater than 5% were analyzed by using univariate Cox regression, followed by separate multivariable Cox regression analyses after adjusting for various clinical factors. Lymph node metastases were most frequently observed in the right upper paratracheal (16.8%) and left gastric artery (13.1%) stations. Multivariable models controlling for clinical factors showed that ypN stage remained a significant independent predictor of survival (N1 vs. N0: hazard ratio [HR], 2.30, 95% confidence interval [CI] 1.38-3.83, P < 0.001; N2 vs. N0: HR, 3.76, 95% CI 2.21-6.38, P < 0.001; N3 vs. N0: HR, 7.14, 95% CI 3.78-13.48, P < 0.001). The model from the multivariable analysis with the highest c-index score, indicating superior discriminatory preference, was ypN stage (c-index, 0.72). The pattern and influence of lymph node metastases after NCT will provide guidance on the extent of lymphadenectomy. Common positive lymph node stations for thoracic ESCC after NCT include the paratracheal, subcarinal, paraesophageal, paracardial, and left gastric artery stations.

Microscopic venous invasion is a predictor of prognosis in patients with esophageal squamous cell carcinoma undergoing ineffective neoadjuvant chemotherapy and surgery.

Neoadjuvant chemotherapy followed by surgery is Japan's most effective treatment modality for advanced thoracic esophageal squamous cell carcinoma. However, the prognosis is not as expected. This study aimed to examine prognostic factors in patients with pathologically ineffective neoadjuvant chemotherapy followed by surgery for esophageal squamous cell carcinoma. We retrospectively analyzed patients who underwent neoadjuvant chemotherapy followed by curative esophagectomy for esophageal squamous cell carcinoma between December 2008 and July 2021. The patients were divided into the neoadjuvant chemotherapy effective group and the neoadjuvant chemotherapy ineffective group according to the pathological diagnosis. Clinicopathological data, prognosis, and recurrence were analyzed. A total of 143 patients (121 males, 22 females; median age, 67years) were included in this study. Of these, 34 patients were classified into the effective group and the remaining 109 patients were assigned to the ineffective group. The ineffective group had significantly worse overall survival and recurrence-free survival than the effective group (p = 0.0192 and p = 0.0070, respectively). In the ineffective group, multivariate analysis demonstrated that microscopic venous invasion was an independent prognostic factor for overall survival (hazard ratio 2.44; 95% confidence interval 1.13-5.30) and recurrence-free survival (hazard ratio 2.43; 95% confidence interval 1.24-4.73). Microscopic venous invasion was associated with poor survival and cancer recurrence in the neoadjuvant chemotherapy ineffective group of patients who underwent esophagectomy for esophageal squamous cell carcinoma.

Neoadjuvant chemoradiotherapy plus tislelizumab followed by surgery for esophageal carcinoma (CRISEC study): the protocol of a prospective, single-arm, phase II trial

BackgroundThe failure rate after neoadjuvant chemoradiotherapy followed by surgery is approximately 34.6%–48% for resectable esophageal carcinoma. Pathologic complete response after neoadjuvant chemoradiotherapy is an important factor in predicting lower recurrence and better survival. Whether the sequential addition of immunotherapy to neoadjuvant chemoradiotherapy will be beneficial to improving the pathologic complete response rate is unknown.MethodsPatients with pathologically confirmed thoracic esophageal squamous cell carcinoma and at clinical T1-2N1-3M0 or T3-4aN0-3M0 (stage II–IVA) according to the eighth edition of American Joint Committee on Cancer staging will be allocated to receive neoadjuvant radiotherapy (41.4 Gy with 23 fractions to planning target volume) with concurrent chemotherapy (albumin-bound paclitaxel, 100 mg/m2, once weekly for five weeks; carboplatin, area under the curve of 2 mg/mL/min, once weekly for five weeks) plus tislelizumab monotherapy sequentially (200 mg every three weeks for three cycles, beginning from the first to the 14th day after the end of radiotherapy). Then, subtotal esophagectomy with two-field lymphadenectomy, including the whole mediastinum and abdomen, will be performed. The primary endpoint for this study is the pathologic complete response rate after neoadjuvant chemoradiotherapy plus tislelizumab.DiscussionThe optimal timing of the combination of immunotherapy and neoadjuvant chemoradiotherapy in esophageal carcinoma is not determined. The results of this phase II trial will be helpful to clarify the safety and efficacy of the sequential addition of tislelizumab after neoadjuvant chemoradiotherapy for locally advanced resectable esophageal carcinoma.Trial registrationThis study was approved on January 26, 2021 and retrospectively registered with ClinicalTrials.gov (NCT04776590) on March 1, 2021.