Surgery For Esophageal Carcinoma Research Articles

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.

ASO Author Reflections: Timing of Surgery and Chemoradiation for Esophageal Squamous Cell Carcinoma.

ASO Author Reflections: Timing of Surgery and Chemoradiation for Esophageal Squamous Cell Carcinoma.

Analysis of Postoperative Complications of Minimally Invasive Surgery for Carcinoma of Oesophagus: A Single Centre Retrospective Cohort Study

Introduction: Traditional transthoracic oesophagectomy is associated with high perioperative morbidity. Minimally Invasive Oesophagectomy (MIE) techniques have been shown to have a decreased incidence of respiratory complications and an improvement in perioperative outcomes, such as length of hospital stay and wound infection rates. Aim: To evaluate the incidence of postoperative respiratory complications, 30-day mortality, and length of hospital stay among patients with carcinoma of the oesophagus undergoing, VideoAssisted Thoracoscopic Surgery (VATS) oesophagectomy. Materials and Methods: A cross-sectional study was conducted in the Department of Anaesthesiology in a new thoracic oncology unit at a Tertiary Cancer care centre, Dr. B. Borooah Cancer Institute, Guwahati, Assam, India. A total of 67 patients with resectable oesophageal cancer who underwent VATS oesophagectomy from September 2019 to December 2021 were included. Patients who had surgery by open thoracotomy and inoperable cases were excluded. The patients’ clinicodemographic profile, intraand postoperative variables, and complications were studied. Descriptive statistics were used for analysis. A p-value ≤0.05 was considered statistically significant at a 5% level of significance. Results: Out of 67 patients, 45 (67.2%) were male, and 22 (32.8%) were female. The age ranged from 33 to 78 years with a median age of 55 years (IQR 47-61). The median body weight was 45 kg (IQR 42-53). Nineteen (28.4%) patients developed postoperative complications, including respiratory distress in 7 (10.4%) and anastomotic leakage in 5 (7.5%) patients. Other complications included symptomatic Coronavirus Disease 2019 (COVID-19) infection, pneumonia, mediastinitis, Multiorgan Dysfunction Syndrome (MODS) with sepsis, seizure and cardiac arrest, and surgical re-exploration. The 30-day mortality was 2.98%. The median length of hospital stay was 19 days (Interquantile Range (IQR) 16-22), which was higher in those with complications (p<0.001). One-lung ventilation was associated with a higher risk of postoperative respiratory complications (p=0.077). Conclusion: VATS oesophagectomy, even in a new thoracic oncology unit, was associated with lower perioperative complications, a shorter hospital length of stay, and decreased mortality compared to historical controls.

Neoadjuvant Chemotherapy Compared with Surgery for Oesophageal Carcinoma: A Retrospective Study and Missing Evidence.

Background: Negative evidence for the use of neoadjuvant chemotherapy (NAC) to treat oesophageal squamous cell carcinoma (ESCC) has been reported in Western countries in the past century. However, in China, most ESCC patients underwent paclitaxel and platinum-based NAC without evidence from local RCTs. Empiricism or a lack of evidence does not necessarily mean that the evidence is negative. However, there was no way to compensate for the missing evidence. The only way to obtain evidence is by conducting a retrospective study using propensity score matching (PSM) to compare the effects of NAC and primary surgery on overall survival (OS) and disease-free survival (DFS) among ESCC patients in China, which is the country with the highest prevalence of ESCC patients. Methods: From January 1, 2015, to December 31, 2018, a total of 5443 patients with oesophageal cancer/oesophagogastric junction carcinoma who underwent oesophagectomy were retrospectively identified at Henan Cancer Hospital. After PSM, 826 patients were selected for the retrospective study and divided into the NAC and primary surgery groups. The median follow-up period was 54.08 months. Toxicity and tumour responses to NAC, intraoperative and postoperative outcomes, recurrence, DFS and OS were analysed. Results: The postoperative complication rates were not significantly different between the two groups. The 5-year DFS rates were 57.48% (95% CI, 52.05% to 62.53%) for the NAC group and 49.93% (95% CI, 44.56% to 55.05%) for the primary surgery group (P=0.0129). The 5-year OS rates were 62.95% (95% CI, 57.63% to 67.79%) for the NAC group and 56.29% (95% CI, 50.99% to 61.25%) for the primary surgery group (P=0.0397). Conclusion: Compared with primary surgery, NAC with paclitaxel and platinum-based chemotherapy and two-field extensive mediastinal lymphadenectomy might be associated with long-term survival benefits among ESCC patients.

163P Neoadjuvant chemoradiotherapy plus tislelizumab followed by surgery for esophageal carcinoma: An interim analysis of the prospective, single-arm, phase II trial

This study aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab followed by surgery for resectable thoracic esophageal squamous cell carcinoma (TESCC).

Clinical and Genomic Analysis of Patients with Short Survival after Surgery for Esophageal Squamous Cell Carcinoma

Background: This study aimed to investigate the prognosis of Chinese patients with esophageal squamous cell carcinoma (ESCC) after surgery and its correlation with genomic alterations (GAs) to identify potential prognostic markers. Methods: The clinical information, pathological specimens, and follow-up information of 50 patients with stage II and III primary ESCC who were surgically resected in the Fourth Hospital of Hebei Medical University from January 2011 to December 2015 were collected in the present study. Based on overall survival (OS), these patients were divided into the short OS group (<3 years) and the long OS group (>4 years). GA detection was performed in patients with ESCC using next-generation sequencing. All categories of GAs were evaluated; the landscape of GAs in patients with ESCC was mapped; and the correlations between clinical characteristics, prognosis, and GAs were analyzed. Results: There was no skew in the distribution of gender, smoking, and adjuvant therapy between the long OS group and the short OS group. A total of 372 GAs were detected in the 50 patients with ESCC, with 7 types of GAs, including insertions, deletions, and copy number variations, and missense mutations occurred most frequently, with a frequency of >50.0%. Tumor protein 53 (TP53; 50/50, 100%) was the most commonly mutated gene in the entire cohort followed by cyclin D1, cyclin-dependent kinase inhibitor 2A (CDKN2A), and fibroblast growth factor 19. More CDKN2A loss (p = 0.098) was detected in the short OS group than in the long OS group. The results of the multivariate analysis after adjustment for clinical factors showed a statistically significant difference in the CDKN2A loss between the two groups. Data obtained from The Cancer Genome Atlas for surgical ESCC revealed that the CDKN2A loss may be responsible for the poorer prognosis in postoperative patients with ESCC. Conclusion: In patients with progressive primary ESCC, the poor postoperative prognosis may be epiphenomenally associated with the CDKN2A loss.

Chemoradiation versus surgery for superficial esophageal squamous cell carcinoma after noncurative endoscopic submucosal dissection: comparison of long-term oncologic outcomes

BackgroundEsophagectomy is the standard adjuvant treatment for superficial esophageal squamous cell carcinoma (SESCC) following noncurative endoscopic submucosal dissection (ESD). However, recent reports have also shown that ESD with adjuvant chemoradiotherapy (CRT) has promising results. This retrospective study aimed to elucidate the efficacy of CRT compared to surgery in patients with SESCC after noncurative ESD.MethodsThis study retrospectively compared the long-term outcomes of patients who received adjuvant treatment with surgery or CRT after noncurative ESD for SESCC.ResultsData were collected from 60 patients who developed SESCC after noncurative ESD, 34 of whom received adjuvant chemoradiotherapy (CRT) and 26 underwent esophagectomy. The median follow-up periods were 46 and 56 months in the CRT and esophagectomy groups, respectively. The median patient age was significantly higher in the CRT group than in the esophagectomy group (69 vs. 65 years, p = 0.0054). CRT was completed in all patients, and the incidence of grade ≥ 3 nonhematologic adverse events was 6%. The overall and disease-free survival did not significantly differ between the two groups.ConclusionsCRT following ESD seems a promising nonsurgical strategy for optimizing the selection of therapies for high-risk SESCC and warrant further investigation.

Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy followed by radical surgery for locally advanced oesophageal squamous cell carcinoma: meta-analysis

The literature lacks robust evidence comparing definitive chemoradiotherapy (dCRT) with neoadjuvant chemoradiotherapy and surgery (nCRS) for oesophageal squamous cell carcinoma (ESCC). This study aimed to compare long-term survival of these approaches in patients with ESCC. A systematic review performed according to PRISMA guidelines included studies identified from PubMed, Scopus, and Cochrane CENTRAL databases up to July 2021 comparing outcomes between dCRT and nCRS for ESCC. The main outcome measure was overall survival (OS), secondary outcome was disease-free survival (DFS). A meta-analysis was conducted using random-effects modelling to determine pooled adjusted multivariable hazard ratios (HRs). Ten studies including 14 092 patients were included, of which 30 per cent received nCRS. Three studies were randomized clinical trials (RCTs) and the remainder were retrospective cohort studies. dCRT and nCRS regimens were reported in six studies and surgical quality control was reported in two studies. Outcomes for OS and DFS were reported in eight and three studies respectively. Following meta-analysis, nCRS demonstrated significantly longer OS (HR 0.68, 95 per cent c.i. 0.54 to 0.87, P < 0.001) and DFS (HR 0.50, 95 per cent c.i. 0.36 to 0.70, P < 0.001) compared with dCRT. Neoadjuvant chemoradiotherapy followed by oesophagectomy correlated with improved survival compared with definitive chemoradiation in the treatment of ESCC; however, there is a lack of literature on RCTs.

Evaluating Neoadjuvant Chemotherapy for Lower Esophageal Squamous Cell Carcinoma by Measuring Esophageal Wall Thickness.

The aim of this study was to evaluate the efficacy of preoperative chemotherapy for stage II-III esophageal squamous cell carcinoma based on an objective computed tomography method. A total of 82 patients who underwent preoperative chemotherapy followed by surgery for advanced esophageal squamous cell carcinoma from January 2006 to June 2019 were included. Treatment effect was evaluated by measuring the esophageal wall thickness before and after neoadjuvant chemotherapy using contrast-enhanced thoracoabdominal computed tomography. The percentage decrease in esophageal wall thickness was calculated using the following formula: reduction (%)=(wall thickness before preoperative chemotherapy - wall thickness after preoperative chemotherapy)/(wall thickness before preoperative chemotherapy)×100. We demonstrated the efficacy of this measurement method and then analyzed which patient factors might affect the treatment effect. Receiver operating characteristic analysis showed the percentage tumor reduction to be a good predictor of histological therapeutic effect (grade ≥2) (area under the curve=0.727). In the multivariate analysis, tumor location (lower versus upper esophagus) was identified as an independent factor associated with tumor reduction (odds ratio=0.15; 95% confidence interval=0.03-0.79; p=0.025). We demonstrated an association between the reduction of esophageal wall thickness in the tumoral area and the histological therapeutic effect of chemotherapy. Secondary analysis showed poorer tumor reduction in patients with lower esophageal cancer than in those with upper esophageal cancer.

Concurrent Chemoradiotherapy Followed by Surgery for Borderline Resectable Esophageal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> This study aimed to clarify the efficacy and safety of induction CRT followed by esophagectomy for borderline resectable esophageal squamous cell carcinoma (BR-ESCC) in which tumors grow very close to the adjacent vital organs. <h3>Materials/Methods</h3> The cohort of this retrospective single-center study included 31 patients who received CRT (41.4 Gy/23 fractions) and radical minimally invasive esophagectomy for T4 BR-ESCC between June 2017 and November 2020. The overall survival (OS), disease-free survival (DFS) and the patterns of recurrence were analyzed. <h3>Results</h3> A total of 14 (45.16%) patients had T4a and 17 (54.84%) had T4b. The median age was 58 (53-65). The clinically involved site were as follows: pleura invasion (15/31), thoracic aorta (14/31), pericardium (13/31), tracheobronchial tree (4/31). The median number of dissected lymph nodes was 28 (16-35). Eight Patients (25.81%) were identified as having a pathologic complete response(pCR). The most surgical complication was anastomotic leakage (16.13%, 5/31) classified as Clavien-Dindo grade II. Respiratory failure was observed in one patient during the early postoperative phase. At a median follow-up interval of 38 months, neither median OS nor DFS was reached. The 3-OS and 3-DFS rates were 62.75% and 61.53%, respectively. Specifically, Patients with pCR showed significantly longer DFS than those who did not (stratified log-rank test: p=0.0301). The OS tended to be better in patients with pCR than in those without pCR (stratified log-rank test: p=0.5635), but not statistically significant. Ten patients (32.3%%) experienced progression during the follow-up period. The recurrence rate of lymph node and distant metastasis were 16.13% (5/31) and 25.81% (8/31). The most frequent metastatic organ was the lung (16.13%) . <h3>Conclusion</h3> The tolerability and efficacy for patients who obtained R0 resection after induction CRT for borderline resectable ESCC was encouraging. The long-term results are worthy of further exploration.

Outcomes of super minimally invasive surgery vs. esophagectomy for superficial esophageal squamous cell carcinoma: a single-center study based on propensity score matching.

Outcomes of super minimally invasive surgery vs. esophagectomy for superficial esophageal squamous cell carcinoma: a single-center study based on propensity score matching.

306. THE ROLE OF ADJUVANT CHEMOTHERAPY AFTER NEOADJUVANT THERAPY FOLLOWED BY SURGERY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract This retrospective study was performed to investigate the efficacy of adjuvant chemotherapy after neoadjuvant therapy followed by surgery in esophageal squamous cell carcinoma (ESCC). The data of 428 patients who received the neoadjuvant therapy and esophagectomy for ESCC between 2003 and 2018 were retrospectively reviewed. The 1:2 propensity score matching was performed to balance the patients’ characteristics. Eighty-three (19.4%) patients received the adjuvant chemotherapy, whereas 345 (80.6%) did not receive the adjuvant chemotherapy. The median follow-up period was 27.04 months (interquartile range: 15.85–62.04 months). The patients who received the adjuvant chemotherapy showed better pulmonary function and ASA score, but there were no differences after propensity score matching. In matched patients, the adjuvant chemotherapy did not improve the OS, but subgroup analysis revealed that 5-year OS improved in ypT + N+ patients by adjuvant chemotherapy (20.2% vs. 27.7%, p = 0.012), whereas the benefit of adjuvant chemotherapy was no observed in ypT0N0, ypT + N0 and ypT0N+. Multivariable analysis showed that ypStage, ASA score and adjuvant chemotherapy (HR 0.462, p = 0.004) was associated with OS in ypT + N+ patients. The freedom from distant metastasis was significantly different according to the adjuvant chemotherapy (27.2% vs. 49.5%, p = 0.039). Adjuvant chemotherapy after neoadjuvant therapy followed by surgery in ypT + N+ ESCC patients might improve the OS by reducing the distant metastasis. The consideration could be given to administration of adjuvant chemotherapy to ypT + N+ ESCC patients with tolerable conditions.

305. SURVIVAL DIFFERENCES ACCORDING TO THE PATHOLOGIC STATUS AFTER NEOADJUVANT THERAPY FOLLOWED BY SURGERY IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract This retrospective study was performed to investigate the survival differences according to the pathologic status after neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery in esophageal squamous cell carcinoma (ESCC). The data of 507 patients who received the neoadjuvant CCRT and esophagectomy for ESCC between 2003 and 2018 were retrospectively reviewed. The mean age was 62.28 ± 8.07 and 473 (93.3%) were male patients. The median follow-up period was 29.24 months (interquartile range: 16.57–49.95 months). 144 (28.4%) patients showed pathologic complete response (ypCR) and 90 (17.8%) patients showed ypCR of primary lesion with residual metastatic lymph nodes (ypT0N+). 107 (33.5%) and 103 (20.3%) patients showed ypT + N+ and ypT + N0, respectively. In patients with residual metastatic lymph nodes, the numbers of metastatic lymph nodes were 1(112, 22.1%), 2(49, 9.7%) and more than 3(100, 19.7%). The 5-year overall survivals (OS) of each group were 71.1%(ypCR), 47.9%(ypT + N0), 51.8%(ypT0N+) and 27.1%(ypT + N+); ypCR patients showed better survival than others and there were no survival differences in 5-year OS between ypT + N0 and ypT0N+ patients (p = 0.811). ypT + N+ patients showed more common locoregional and distant metastasis. The 5-year freedom from distant metastasis were different according to pathologic status; 83.1%(ypCR), 69.4%(ypT + N0), 59.1%(ypT0N+) and 44.6%(ypT + N+). The numbers of residual metastatic lymph nodes were related to the distant metastasis (HR1.083, p &amp;lt; 0.001) ypCR offers long-term survival in patients without nodal metastases, but the survival significantly deteriorates with the presence of residual primary lesion and nodal metastases. Follow-up strategies and indication of additional postoperative therapy could be guided according to the pathologic status after neoadjuvant CCRT followed by surgery.

Real-time Tracking and Classification of Tumor and Nontumor Tissue in Upper Gastrointestinal Cancers Using Diffuse Reflectance Spectroscopy for Resection Margin Assessment

Cancers of the upper gastrointestinal tract remain a major contributor to the global cancer burden. The accurate mapping of tumor margins is of particular importance for curative cancer resection and improvement in overall survival. Current mapping techniques preclude a full resection margin assessment in real time. To evaluate whether diffuse reflectance spectroscopy (DRS) on gastric and esophageal cancer specimens can differentiate tissue types and provide real-time feedback to the operator. This was a prospective ex vivo validation study. Patients undergoing esophageal or gastric cancer resection were prospectively recruited into the study between July 2020 and July 2021 at Hammersmith Hospital in London, United Kingdom. Tissue specimens were included for patients undergoing elective surgery for either esophageal carcinoma (adenocarcinoma or squamous cell carcinoma) or gastric adenocarcinoma. A handheld DRS probe and tracking system was used on freshly resected ex vivo tissue to obtain spectral data. Binary classification, following histopathological validation, was performed using 4 supervised machine learning classifiers. Data were divided into training and testing sets using a stratified 5-fold cross-validation method. Machine learning classifiers were evaluated in terms of sensitivity, specificity, overall accuracy, and the area under the curve. Of 34 included patients, 22 (65%) were male, and the median (range) age was 68 (35-89) years. A total of 14 097 mean spectra for normal and cancerous tissue were collected. For normal vs cancer tissue, the machine learning classifier achieved a mean (SD) overall diagnostic accuracy of 93.86% (0.66) for stomach tissue and 96.22% (0.50) for esophageal tissue and achieved a mean (SD) sensitivity and specificity of 91.31% (1.5) and 95.13% (0.8), respectively, for stomach tissue and of 94.60% (0.9) and 97.28% (0.6) for esophagus tissue. Real-time tissue tracking and classification was achieved and presented live on screen. This study provides ex vivo validation of the DRS technology for real-time differentiation of gastric and esophageal cancer from healthy tissue using machine learning with high accuracy. As such, it is a step toward the development of a real-time in vivo tumor mapping tool for esophageal and gastric cancers that can aid decision-making of resection margins intraoperatively.

The safety of neoadjuvant chemotherapy combined with non-tube nofasting fast-track surgery for esophageal carcinoma.

Our non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective to combine with neoadjuvant chemotherapy for McKeown minimally invasive esophagectomy. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.ObjectivesTo evaluate the safety of early oral feeding (EOF) combined with neoadjuvant chemotherapy (NAC) of esophagectomy.Summary Background DataOur non-tube no fasting (early oral feeding and no nasogastric tube) fast-track surgery (FTS) was safe and effective for primary surgery esophageal cancer patients.MethodsWe retrospectively evaluated consecutive patients who underwent non-tube no fasting and McKeown minimally invasive (MIE). They were divided into two groups: one received NAC, and the other received primary surgery. Complications after the operation, postoperative CRG complications, operative time, operative bleeding, and length of stay were evaluated.ResultsBetween 01/2014 and 12/2017, there hundred and eighty two consecutive patients underwent MIE with total two-field lymphadenectomy under the non-tube no fasting fast-track surgery program. A total of 137 patients received NAC, and 245 accepted primary surgery. Propensity score matching was used to compare NAC patients with 62 matched patients from each group. The NAC group had a similar number of total complications as the primary surgery group (32.26% in the primary surgery group vs. 25.81% in the NAC group; p=0.429) and had the same median postoperative hospitalization duration (8 days, p=0.723).ConclusionsAfter McKeown MIE, the patients receiving NAC combined with “non-tube no fasting” FTS had a similar incidence of postoperative complications outcomes as those without NAC. In addition, the two groups were similar in terms of the recovery time, hospital discharge day, and early resumption of oral feeding.

Immunohistochemical analyses of paraffin-embedded sections after primary surgery or trimodality treatment in esophageal carcinoma

BackgroundThe microscopic tumor extension before, during or after radiochemotherapy (RCHT) and its correlation with the tumor microenvironment (TME) are presently unknown. This information is, however, crucial in the era of image-guided, adaptive high-precision photon or particle therapy. Materials and methodsIn this pilot study, we analyzed formalin-fixed paraffin-embedded (FFPE) tumor resection specimen from patients with histologically confirmed squamous cell carcinoma (SCC; n = 10) or adenocarcinoma (A; n = 10) of the esophagus, having undergone neoadjuvant radiochemotherapy followed by resection (NRCHT + R) or resection (R)]. FFPE tissue sections were analyzed by immunohistochemistry regarding tumor hypoxia (HIF-1α), proliferation (Ki67), immune status (PD1), cancer cell stemness (CXCR4), and p53 mutation status. Marker expression in HIF-1α subvolumes was part of a sub-analysis. Statistical analyses were performed using one-sided Mann-Whitney tests and Bland-Altman analysis. ResultsIn both SCC and AC patients, the overall percentages of positive tumor cells among the five TME markers, namely HIF-1α, Ki67, p53, CXCR4 and PD1 after NRCHT were lower than in the R cohort. However, only PD1 in SCC and Ki67 in AC showed significant association (Ki67: p = 0.03, PD1: p = 0.02). In the sub-analysis of hypoxic subvolumes among the AC patients, the percentage of positive tumor cells within hypoxic regions were statistically significantly lower in the NRCHT than in the R cohort across all the markers except for PD1. ConclusionIn this pilot study, we showed changes in the TME induced by NRCHT in both SCC and AC. These findings will be correlated with microscopic tumor extension measurements in a subsequent cohort of patients.

A survey of the clinical outcomes of cervical esophageal carcinoma surgery focusing on the presence or absence of laryngectomy using the National Clinical Database in Japan.

One upside of cervical esophageal carcinoma is that radical surgery can be performed by laryngectomy, even for tumors with tracheal invasion. However, this approach drastically reduces the quality of life, such as by losing the vocal function. Cervical esophageal carcinoma is rare, and no comprehensive reports have described the current state of surgery. Using a Japanese nationwide web-based database, we analyzed the surgical outcomes of cervical esophageal carcinoma to evaluate the impact of larynx-preserving surgery. Based on the Japan National Clinical Database, 215 surgically treated cases of cervical esophageal carcinoma between January 1, 2018, and December 31, 2019, were enrolled. Clinical outcomes were compared between the larynx-preserved group and the laryngectomy group. Ninety-four (43.7%) patients underwent larynx-preserving surgery. A total of 177 (82.3%) patients underwent free jejunum reconstruction. More T4b patients and more patients who underwent preoperative radiotherapy were in the laryngectomy group. There were no significant differences in the frequency and the severity of morbidities between the two groups. However, in the laryngectomy group, in-hospital death within 30days after surgery was observed in 1 patient, and the postoperative hospital stay was significantly longer (P = 0.030). In the larynx-preserved group, recurrent nerve paralysis was observed in 24.5%. Re-operation (35.3%, P = 0.016), re-intubation (17.6%, P = 0.019) and tracheal necrosis (17.6%, P = 0.028) were significantly more frequent in patients who underwent pharyngolaryngectomy with total esophagectomy and gastric tube reconstruction than in others. Larynx-preserving surgery was therefore considered to be feasible because it was equivalent to laryngectomy regarding the short-term surgical outcomes.

Conversion surgery following immuno-chemotherapy in initially-unresectable esophageal squamous cell carcinoma: A real-world multicenter study.

e16045 Background: Currently, the real-world evidence is not available to support the practice of induction immunochemotherapy (iIC) plus conversion surgery for initially-unresectable esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the feasibility, safety and effectiveness of conversion surgery following iIC for advanced ESCC in a real-world scenario. Methods: In this multi-center, single-arm, real-world study (NCT04822103), patients who had unresectable cT4b ESCC tumors with evident involvement of the adjacent organs (aorta, trachea, or bronchus) or had multi-station, bulky lymphadenopathy were enrolled across eight medical centers in China. All patients received programmed death receptor-1 (PD-1) inhibitor plus chemotherapy every three weeks. Radiologcal assessment was performed for patients who completed at least two cycles of immunochemotherapy. In general, patients with significant relief of cancer-related clinical symptoms and radiological complete response/partial response disease were deemed surgical candidates. The primary endpoints were the objective response rate (ORR) per RECIST version 1.1 and safety profile per CTCAE version 5.0. Results: Between Nov 2019 and June 2021, 155 patients were enrolled in the final analysis. The numbers of patients with pre-treatment clinical stage III, and IVA were 21 (13.5%) and 134 (86.5%), respectively. Upon the completion of preoperative treatment, 6 (3.9%) patients achieved radiological complete response (CR), 92 (59.4%) achieved partial response (PR), and 45 (29.0%) achieved stable disease (SD), yielding an ORR and DCR of 63.3% and 92.3%, respectively. Esophagectomy was then offered to 116 patients who were considered suitable for surgery, yeilding a conversion rate of 74.8%. 109 out of 116 patients achieved R0 resection. Pathological complete response (pCR) of the primary tumor was observed in 26 (22.4%) patients, with 25 (21.6%) of them achieving pCR in both primary tumor and metastatic lymph nodes. Most patients (111/116, 95.7%) had a downstaging in tumor invasion depth. However, downstaging of nodal metastasis was observed in 48 (48/116, 41%) patients. Thirteen patients (13/116, 11.2%) had progressive nodal response. Among the treated patients, 69.0% (107/155) patients experienced at least one treatment-related adverse event (TRAEs), while 29% (49/155) had grade three or higher (G ≥ 3) TRAEs, including leukopenia (20/155, 12.9%), neutropenia (18/155, 11.6%), rash (12/155, 7.7%), diarrhea (6/155, 3.9%), and infection (6/155, 3.9%). Conclusions: We demonstrated that conversion surgery following immunochemotherapy is feasible, safe and effective for initially-unresectable ESCC patients. Further larger-scale studies are needed to establish the standard-of-care use of iIC in the preoperative settings for initially-unresectable ESCC patients.

Evaluation of Neoadjuvant Chemoradiotherapy Followed by Surgery for Borderline Resectable Esophageal Squamous Cell Carcinoma.

It is occasionally difficult to diagnose cT3 or cT4b using imaging examinations for esophageal cancer. The optimal treatment strategy for borderline resectable esophageal squamous cell carcinoma (BR-ESCC) is unclear. We included 131 patients with cT3 ESCC who received neoadjuvant chemoradiotherapy (NCRT) followed by surgery. The patients were classified as having definitive cT3 (D-cT3) or borderline resectable cT3 (BR-cT3), based on presence of undeniable adjacent organ invasion on pretreatment CT. Surgical outcomes and prognoses were compared among patients with D-cT3 and BR-cT3 tumors, and the risk factors for non-R0 resection were assessed. Ninety and 41 patients were classified as D-cT3 and BR-cT3, respectively. Although BR-cT3 had a significantly higher non-R0 resection rate than D-cT3 (D-cT3 3.7%; BR-cT3 14.6%), BR-cT3 was not correlated with shorter overall survival (OS) (D-cT3 5-year OS, 50.8%; BR-cT3 5-year OS 38.4%; p = 0.234). Conversely, non-R0 resection was significantly associated with poor OS (R0 resection 5-year OS 48.8%; non-R0 resection 5-year OS 22.2%; p = 0.031). Cox regression analysis of OS demonstrated that BR-cT3 was not a prognostic factor. In the analysis of risk factors for non-R0 resection, BR-cT3 (p = 0.027), suspected invasion of the trachea or bronchus (p = 0.046), and high SUVmax of the primary lesion after NCRT (p = 0.002) were risk factors. NCRT followed by surgery achieved a relatively high R0 resection rate and an almost equal overall survival rate for BR-cT3 compared with D-cT3 ESCC. Thus, NCRT followed by surgery is an effective treatment strategy for patients with BR-cT3 ESCC.