Resectable Esophageal Carcinoma Research Articles

345. PERI-OPERATIVE SELECTIVE DECONTAMINATION OF THE DIGESTIVE TRACT TO PREVENT SEVERE INFECTIOUS COMPLICATIONS AFTER ESOPHAGECTOMY: A RANDOMIZED MULTICENTER CLINICAL TRIAL

Abstract Protocol presentation Rationale: Esophagectomy is a complex surgical procedure, associated with significant morbidity and mortality rates. Most postoperative complications are caused by infections (10–30%). These are thought to arise from (micro-)aspiration of bacteria residing in the oropharyngeal and gastrointestinal (GI) tract, leading to (respiratory) infections. Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic strategy that aims to prevent postoperative infections. Pathogenic aerobic gram-negative rods and yeasts are reduced, while anaerobic, protective microbiota are preserved. SDD has been shown to lower the risk for respiratory infections in an intensive care setting. Establishing SDD as effective addition to the standard care of esophagectomy patients is expected to increase their chance of survival. Objective Robust and prospective evaluation of SDD after esophagectomy as a protective strategy reducing postoperative pneumonia and other infectious complications, anastomotic leakage and mortality. Study design and population A randomized, controlled, open-label, multicentre trial, including 854 patients with primary resectable esophageal carcinoma ((y)cT1-4a N0-3 M0) planned for transthoracic esophagectomy. Intervention The intervention group receives SDD treatment additional to standard care. An oral suspension (10ml) containing amphotericin B (50 mg/ml), colistin sulphate (10 mg/ml), and tobramycin (8 mg/ml). Patients take the oral suspension four times daily for one week, starting three days prior to the surgery. On the day of surgery, intake is limited to an early morning and a late evening dose. All other facets of care are equal to the control group (standard care without SDD). Two microbial samples will be taken from the esophageal resection specimen (one proximal and one from the distal part) for culture to evaluate effectiveness and compliance of SDD application in control as well as in the intervention group. Furthermore, all participants will be asked to keep a diary. Main study parameters The cumulative incidence of postoperative pneumonia within 30 days after surgery. Secondary study parameters The cumulative incidence of all postoperative complications and re-operation within 30 days after surgery, all- cause mortality within 90 days, length of stay and readmissions within 6 months and quality of life, direct and indirect costs; a week before, 30 days-, 3 months and 6 months after surgery.

Challenges in early detection and endoscopic resection of esophageal cancer: There is a long way to go.

The publication by Qu et al provided a comprehensive discussion about the epidemiology, etiology, histopathology, early detection, and endoscopic treatment of esophageal carcinoma (EC) and summarized the progress in the advanced technologies for screening and endoscopic resection for EC. In this editorial, we will provide deeper insight into the challenges that hinder practical application of these advanced technologies along with the role of these technologies in upper endoscopy quality. More efforts need to be made to overcome the challenges and add the value of these technologies in upper endoscopy quality. Clinical outcomes of management strategies after noncurative endoscopic dissection for early EC patients need further investigation. The experiences with noncurative endoscopic resection of other organs may have certain implications for noncurative resection of early EC.

Fecal, Duodenal and Tumor Microbiota Composition of Esophageal Carcinoma Patients, a Longitudinal Prospective Cohort.

The microbiome has been associated with chemotherapy and immune checkpoint inhibitor (ICI) efficacy. How this pertains to resectable esophageal carcinoma (EC) is unknown. Our aim was to identify microbial signatures in resectable EC associated with response to neoadjuvant chemoradiotherapy (nCRT) with or without ICI. From two prospectively collected EC cohorts (n = 172 in total) treated with nCRT alone (n = 132) or a combination of nCRT and ICI (n = 40), fecal samples were available at baseline, during treatment, and pre-surgery. Additionally, in the ICI treated patients, tumor and duodenal snap frozen biopsies were collected over time. Fecal, tumor and duodenal DNA were extracted for 16S rRNA sequencing. Associations were investigated between microbiome composition pathological complete response (pCR) and progression-free survival (PFS). There was a significant shift in the microbiota profile of the fecal, tumor and duodenal microbiota over time. In the total cohort, patients with a pCR had a stable fecal alpha diversity, while the diversity of poor responders decreased during treatment, p = 0.036. Pre-surgery, lower alpha diversity (<4.12) was related to worse PFS, log-rank p = 0.025. Baseline tumor biopsies of patients with short PFS had more Fusobacterium. A low baseline duodenal alpha diversity (<3.96) was associated with worse PFS, log-rank p = 0.012. Lower intestinal alpha diversity was associated with worse response and survival of EC patients. In tumor biopsies Fusobacterium was more abundant in patients with poor PFS. After further mechanistic validation, these findings may aid in response prediction and the design of novel microbiome modulating treatments for EC patients.

Distinct tumor microbiome and metabolomic profiles to inform responses of patients with esophageal cancer to neoadjuvant chemoradiotherapy and immunotherapy.

4084 Background: Preclinical and clinical data indicate that neoadjuvant chemoradiotherapy (CRT) may prime an anti-tumor immunological response in esophageal cancer driven by intratumoral CD8+ T cells. However, responses to neoadjuvant therapy can vary widely across patients. The microbiome, a novel and potentially modifiable biomarker of immunotherapy response, may inform neoadjuvant response. Methods: Fecal and tumor samples were collected from patients with stage II-III resectable distal esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immunotherapy followed by chemoradiotherapy (CRT) and immunotherapy (IO). Patients on arm A (n=15) received 2 cycles of induction with nivolumab plus 3 additional cycles with CRT. Patients on arm B (n=10) received nivolumab and relatlimab on a similar induction schedule, but concurrent IO and CRT resulted in immune related adverse events and a protocol amendment to CRT (NCT03044613). We examined fecal (n=19) and tumor (n=12) patient samples across both arms using 16S rRNA amplicon sequencing and high-resolution taxonomic assignment. Additionally, fecal samples were analyzed using an untargeted panel (General Metabolics) and pathway analysis was performed using Metaboanalyst (v6.0). Results: The fecal microbiome of patients with pathological complete response (pCR) grouped in distinct clusters compared to patients without pathological complete response (non-pCR) using Bray-Curtis (p &lt; 0.001). Patients with &gt;10% and &lt;10% residual tumor grouped similarly but were significantly different from patients with 0% residual tumor (p &lt; 0.001). On a linear discriminant axis, the top 10 abundant bacteria were significantly increased in pCR compared to non-pCR (p &lt; 0.001). After FDR correction, six bacteria had significantly differing abundances. Bacteroides finegoldii, Paraprevotella clara, Ruminococcus callidus, and Roseburis inulinivorans were significantly enriched in pCR patients. Clostridiales and Bacteroides were significantly enriched in non-pCR patients. Fecal metabolomic analysis demonstrated six significant metabolites: in non-pCR, ropinirole, valine, phenylalanine, and isoleucine were enriched; in pCR, C16cer and D-urobilinogen were enriched (p &lt; 0.05). Patients with improved neoadjuvant response had significantly higher abundances of Bacteroides and corresponding C16cer levels. Pathway analysis revealed significant involvement in aminoacyl-tRNA biosynthesis and sphingolipid metabolism. Conclusions: Patients with complete responses to combined CRT and IO for operable esophageal cancer had distinct fecal microbiome profiles as well as metabolomic pathways. These results may be useful to further characterize and predict patients who have improved responses to neoadjuvant therapy and serve as a basis for therapeutic intervention.

A prospective single-center, single-arm, open-label, phase II study of sintilimab and anlotinib combined with chemotherapy in neoadjuvant treatment of resectable esophageal cancer.

Antiangiogenic treatment and immunochemotherapy effectively treat patients with advanced esophageal cancer. However, there remains a dearth of studies concerning neoadjuvant therapy for resectable esophageal cancer. The study focused on patients with T2-4NxM0 resectable esophageal carcinoma. Neoadjuvant treatment involved administering anlotinib (10 mg orally, once a day, 2 weeks on and 1 week off) for antiangiogenesis and sintilimab (200 mg) and chemotherapy for three cycles. Surgical treatment was performed 4-6 weeks after the last chemotherapy cycle was completed. The primary endpoints assessed were pathological complete response (pCR) and safety. Out of the 34 screened patients, 17 were successfully enrolled in the study, and 14 completed the entire treatment process. The pCR was 35.3% (6/17). However, two patients experienced mortality. The occurring rate of grade 3 or higher complications after the surgery was 78.6% (11/14) according to Clavien-Dindo classification. Specifically, anastomotic leakage was observed in 57.1% (8/14) of the patients. Compared to neoadjuvant chemotherapy, the current regimen demonstrated improved pCR. However, it did not show significant improvement compared to immunochemotherapy. It is essential to exercise caution when using this treatment approach in patients with esophageal cancer as it might increase postoperative complications, especially anastomotic leakage.

Treatment options for neoadjuvant strategies of esophageal squamous cell carcinoma (Review).

Compared with postoperative adjuvant therapy, neoadjuvant therapy has more potential advantages, such as decreasing tumor stage, killing micrometastatic cells. Because of these advantages, neoadjuvant therapy is recommended for numerous types of tumor, such as breast, lung and rectal cancer. To determine the role of neoadjuvant therapy on overall survival and adverse for patients with resectable esophageal carcinoma. we summarized clinical studies on 7 types of neoadjuvant therapies in this review. Currently, patients with esophageal cancer (EC) in China mainly receive postoperative treatment with <30% of patients receiving neoadjuvant therapy. One reason for the limited use of neoadjuvant therapy in China is inaccurate staging based on imaging and neoadjuvant treatment may increase difficulties in surgery. After neoadjuvant therapy, there may be tissue edema, blurry surgical field of view and unclear tissue gaps, resulting in greater difficulty in surgical procedures. However, oncologists are interested in neoadjuvant treatment, especially neoadjuvant immunotherapy to treat EC. Concurrent chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) is the most common neoadjuvant treatment regimen and increases the pathological complete response (pCR) and 5- and 10-year survival rates. Preoperative induction chemotherapy and sequential concurrent chemoradiotherapy are currently the most widely treatments used in clinical practice in China. However, this treatment strategy does not yield long-term survival. The pCR rate of neoadjuvant immunotherapy is greater than that of concurrent chemoradiotherapy but, to the best of our knowledge, no evidence of long-term survival benefit has been found in phase I and II clinical trials. Neoadjuvant treatment should be considered for patients with locally advanced ESCC.

OGC O09 Fluorescence lymphography using indocyanine green in the prevention of chyle leakage after minimally invasive esophagectomy

Abstract Background For oncological reasons, the thoracic duct is resected during esophagectomy for cancer. Its anatomy and vulnerability render it prone to injury and mainly side branches and collaterals are often hard to visualize. Chyle leakage is one of the most challenging complications in esophagectomy, with an incidence of 14-21%. The clinical implications for patients are prolonged thoracic drainage and hospital admission, additional reinterventions, unpleasant dietary restrictions, and decreased long-term survival. Fluorescence lymphography using indocyanine green (ICG) can accurately visualize the thoracic duct and collaterals, which may possibly reduce the incidence of chyle leakage and intra-operative detected chyle leakage can be treated directly. Methods A prospective observational cohort study will be performed. Patients aged over 18 years with resectable (cT1-4a, N0-3, M0) esophageal carcinoma undergoing a minimally invasive esophagectomy will be included. The primary endpoint of the study is postoperative chyle leakage. Secondary endpoints are overall morbidity and mortality, nature of dietary restrictions, reinterventions, hospital costs, 2 year survival rate and quality of life. Twenty-five milligram of ICG is dissolved in 10 ml of sterile water, obtaining a solution of 2.5 mg ICG per mL. In the McKeown esophagectomy, before the thoracic phase, the surgeon administers a bilateral bolus of 2 mL ultrasound-guided into inguinal lymph nodes. In an Ivor Lewis esophagectomy, 2mL of reconstituted ICG will be injected into the small bowel mesenteric root just under the peritoneum of the mesentery, at the level where the jejunostomy is placed. Additionally, 50 mL of cream is enterally administered through the just established feeding jejunostomy. Subsequently, the operating area is inspected for chyle leakage with fluorescence lymphography after thoracic duct ligation and just before terminating the procedure. Results We aim to include 50 patients to assess the feasibility of fluorescent lymphography using ICG and enteral cream to prevent chyle leakage after minimally esophagectomy. Inclusion is ongoing. At this time 39 of 50 patients are included. Results will be expected before the congress. Conclusions It is hypothesized that as a result of this technique the patients will benefit from lower incidence of postoperative chyle leakage, shorter thoracic drainage, reduced hospital admission, reduced dietary restriction, less re-interventions, and improved overall survival.

Effect of percutaneous endoscopic gastrostomy prior to oesophageal cancer surgery on postoperative wound complications in patients: A meta-analysis.

It is still a matter of controversy whether percutaneous endoscopic gastrostomy(PEG) should be used prior to the operation for the purpose of feeding the patient with resectable oesophageal carcinoma (EC). Comparison was made between EC and preoperatively treated PEG and non-preoperative PEG. An extensive literature review has been conducted to determine the results about PEG and No-PEG trials. In this paper, we chose 4 papers out of 407 of them through a strict selection process. In this trial, there were 1027 surgical cases of oesophagus carcinoma, 152 with PEG pre-surgery and 875 without PEG. The total sample size ranged from 14 to 657. Two studies showed that there was no statistically significant difference in the occurrence of postoperative wound infection among PEG and No-PEG(OR, 1.03; 95% CI, 0.38, 2.80 p = 0.96), there was no statistical significance in the likelihood of anastomotic leak among PEG after surgery compared to No-PEG in 4 trials (OR, 1.13; 95% CI, 0.62-2.07 p = 0.69), and there were no statistical differences between PEG and No-PEG before operation on anastomotic stricture for esophagectomy(OR, 0.70; 95% CI, 0.31-1.56 p = 0.38). No wound or anastomosis complications were observed in the PEG group. Thus, PEG preoperatively is an effective and safe procedure without any harmful influence on gastrointestinal structure or anastomosing. It can be applied to patients with oesophagus carcinoma who have a high risk of undernutrition. Nevertheless, because of the limited number of randomized controlled trials in this meta-analysis, caution should be exercised in their treatment. More high-quality research involving a large sample is required to confirm the findings.

322. FLUORESCENCE LYMPHOGRAPHY USING INDOCYANINE GREEN IN THE PREVENTION OF CHYLE LEAKAGE AFTER MINIMALLY INVASIVE ESOPHAGECTOMY

Abstract Background Chyle leakage is one of the most challenging complications in esophagectomy, with an incidence of 14–21%. The clinical implications for patients are prolonged thoracic drainage and hospital admission, additional reinterventions, unpleasant dietary restrictions, and decreased long-term survival. The anatomy and vulnerability of the thoracic duct render it prone to injury, and mainly side branches and collaterals are often hard to visualize. Fluorescence lymphography using indocyanine green (ICG) can accurately visualize the thoracic duct, which may possibly reduce the incidence of chyle leakage and intra-operative detected chyle leakage can be treated directly. Methods A prospective observational cohort study is performed. Patients aged over 18 years with resectable (cT1-4a, N0–3, M0) esophageal carcinoma undergoing a minimally invasive esophagectomy are included. The primary endpoint of the study is postoperative chyle leakage. Secondary endpoints are overall morbidity and mortality, nature of dietary restrictions, reinterventions, hospital costs, 2 year survival rate and quality of life. Twenty-five milligram of ICG is dissolved in 10 mL of sterile water, obtaining a solution of 2.5 mg ICG per mL. In the McKeown esophagectomy, before the thoracic phase, the surgeon administers a bilateral bolus of 2 mL ultrasound-guided into inguinal lymph nodes. In an Ivor Lewis esophagectomy, 2 mL of reconstituted ICG will be injected into the small bowel mesenteric root just under the peritoneum of the mesentery, at the level where the jejunostomy is placed. Additionally, 50 mL of cream is enterally administered through the just established feeding jejunostomy. Subsequently, the operating area is inspected for chyle leakage with fluorescence lymphography after thoracic duct ligation and just before terminating the procedure. Results We aim to include 50 patients to assess the feasibility of fluorescent lymphography using ICG and enteral cream to prevent chyle leakage after minimally esophagectomy. Inclusion is ongoing, at this time, 31 of 50 patients are included. Results will be expected before the congress. Conclusion It is hypothesized that as a result of this technique the patients will benefit from lower incidence of postoperative chyle leakage, shorter thoracic drainage, reduced hospital admission, reduced dietary restriction, less re-interventions, and improved overall survival.

Different gastric tubes in esophageal reconstruction during esophagectomy.

Esophagectomy is currently the mainstay of treatment for resectable esophageal carcinoma. Gastric grafts are the first substitutes in esophageal reconstruction. According to the different tailoring methods applied to the stomach, gastric grafts can be classified as whole stomach, subtotal stomach and gastric tube. Gastric-tube placement has been proven to be the preferred method, with advantages in terms of postoperative complications and long-term survival. In recent years, several novel methods involving special-shaped gastric tubes have been proposed, which have further decreased the incidence of perioperative complications. This article will review the progress and clinical application status of different types of gastric grafts from the perspectives of preparation methods, studies of anatomy and perioperative outcomes, existing problems and future outlook.

Survival and perioperative outcomes of octo- and nonagenarians with resectable esophageal carcinoma.

The outcomes of different treatment modalities for patients aged 80 and above with locally advanced and resectable esophageal carcinoma are not well described. The aim of this study was to explore survival and perioperative outcomes among this specific group of patients. A retrospective, cohort analysis was performed on a prospectively maintained esophageal cancer database from the McGill regional upper gastroinestinal cancer network. Between 2010 and 2020, all patients ≥80years with cT2-4a, Nany, M0 esophageal carcinoma were identified and stratified according to the treatment modality: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT); definitive CRT (dCRT); upfront surgery; palliative CT/RT; or best supportive care (BSC). Of the 162 patients identified, 79 were included in this study. The median age was 83years (80-97), most were cT3 (73%), cN- (56%), and had adenocarcinoma (62%). Treatment included: nCT/nCRT (16/79, 20%); surgery alone (19/79, 24%); dCRT (12/29, 15%); palliative RT/CT (27/79, 34%); and BSC (5/79, 6%). Neoadjuvant treatment was completed in 10/16 (63%). Of the 35/79 who underwent surgery, major complications occurred in 13/35 (37%) and 90-day mortality in 3/35 (9%). Overall survival (OS) for the cohort at 1- and 3-years was 58% and 19%. Among patients treated with nCT/nCRT, this was 94% and 46% respectively. Curative intent treatment (nCT/nCRT/upfront surgery/dCRT) had significantly increased 1- and 3- year OS compared with non-curative treatment (76%/31% vs. 34%/3.3%). Multimodal standard of care treatment is feasible and safe in select octo/nonagenarians, and may be associated with improved OS. Age alone should not bias against treatment with curative intent.

Individual Participant Data Network Meta-Analysis of Neoadjuvant Chemotherapy or Chemoradiotherapy in Esophageal or Gastroesophageal Junction Carcinoma.

The optimal neoadjuvant treatment for resectable carcinoma of the thoracic esophagus (TE) or gastroesophageal junction (GEJ) remains a matter of debate. We performed an individual participant data (IPD) network meta-analysis (NMA) of randomized controlled trials (RCTs) to study the effect of chemotherapy or chemoradiotherapy, with a focus on tumor location and histology subgroups. All, published or unpublished, RCTs closed to accrual before December 31, 2015 and having compared at least two of the following strategies were eligible: upfront surgery (S), chemotherapy followed by surgery (CS), and chemoradiotherapy followed by surgery (CRS). All analyses were conducted on IPD obtained from investigators. The primary end point was overall survival (OS). The IPD-NMA was analyzed by a one-step mixed-effect Cox model adjusted for age, sex, tumor location, and histology. The NMA was registered in PROSPERO (CRD42018107158). IPD were obtained for 26 of 35 RCTs (4,985 of 5,807 patients) corresponding to 12 comparisons for CS-S, 12 for CRS-S, and four for CRS-CS. CS and CRS led to increased OS when compared with S with hazard ratio (HR) = 0.86 (0.75 to 0.99), P = .03 and HR = 0.77 (0.68 to 0.87), P < .001 respectively. The NMA comparison of CRS versus CS for OS gave a HR of 0.90 (0.74 to 1.09), P = .27 (consistency P = .26, heterogeneity P = .0038). For CS versus S, a larger effect on OS was observed for GEJ versus TE tumors (P = .036). For the CRS versus S and CRS versus CS, a larger effect on OS was observed for women (P = .003, .012, respectively). Neoadjuvant chemotherapy and chemoradiotherapy were consistently better than S alone across histology, but with some variation in the magnitude of treatment effect by sex for CRS and tumor location for CS. A strong OS difference between CS and CRS was not identified.

Treg cells and the response to neoadjuvant chemotherapy combined with immunotherapy in resectable esophageal squamous carcinoma.

e14626 Background: More and more studies focus on the neoadjuvant chemotherapy combined with immunotherapy (chemo-immunotherapy) in resectable esophageal squamous carcinoma (ESCC). Herein, we aimed to evaluate the efficacy and safety of neoadjuvant programmed cell death protein 1 inhibitors with chemotherapy and explore tumor microenvironment (TME) profiles. Methods: Patients with previously untreated, resectable, stage III ESCC in the third affiliated hospital of Soochow University were enrolled. Each patient received two-four cycles of neoadjuvant chemo-immunotherapy before surgical resection. The TME profiles of formalin-fixed paraffin-embedded tumor samples at baseline were evaluated by multiplex immunofluorescence to discover novel biomarkers of response to neoadjuvant chemo-immunotherapy. Results: Twenty patients were included, all of whom underwent R0 resection. 85% (17/20) of patients underwent 2 cycles of neoadjuvant therapy. TP53 (13/20,65%) was were high-frequency mutated gene, followed by CDKN2A (5/20,25.0%) and PIK3CA (3/20, 15.0%). PD-L1 positive (TPS≥1%) was found in only 3 patients. Postoperative pathological evaluation showed that 18 patients (90.0%) were major pathologic response (MPR), of which 5 patients (28.0%) achieved pathological complete response (pCR). Neoadjuvant therapy has acceptable side effects. TME profiles at baseline showed no significant correlation between PD-L1 and pathological response. The density of Treg cell in the tumor area was significantly lower in pCR patients than in MPR patients (P=0.0302). Conclusions: Neoadjuvant chemo-immunotherapy was well tolerated and was effective therapy for resectable ESCC. Treg cells may serve as potential predictive biomarkers.

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.

"Accidental Severance of Peripherally Inserted Central Catheter Migration into Azygos Vein During Resection of Esophageal Carcinoma"

"Accidental Severance of Peripherally Inserted Central Catheter Migration into Azygos Vein During Resection of Esophageal Carcinoma"

Efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or gastroesophageal junction carcinoma: A pooled analysis of prospective clinical trials.

Neoadjuvant chemoradiotherapy (NCRT) plus radical esophagectomy is currently the standard treatment for resectable esophageal or gastroesophageal junction (GEJ) carcinoma. The aim of this study is to evaluate the efficacy and safety of neoadjuvant immunotherapy in resectable esophageal or GEJ carcinoma. Prospective clinical trials investigating efficacy and/or safety of neoadjuvant immunotherapy with immune checkpoint inhibitors (ICIs) followed by radical esophagectomy in patients with newly diagnosed resectable esophageal or GEJ carcinoma were identified through literature search. Quality assessment was performed by using the Newcastle-Ottawa scale. Preliminary treatment outcomes of pathologically complete response (pCR, ypT0N0) and grade 3-4 adverse effects (AEs) were pooled together and then compared with standard NCRT of the historical control CROSS study by Chi-square (χ2) test. A two-sided P value < 0.05 was considered statistically significant. A total of 17 eligible non-randomized trials with 455 participants were included into analysis. The most common primary endpoint was pCR (n = 7, 41%), and the median sample size and follow-up period was 23 patients and 7.9 months, respectively. For patients receiving neoadjuvant immunotherapy, the overall pCR, R0 resection, and grade 3-4AE rates were 33.2%, 95.5%, and 35.1%, respectively. For esophageal squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), neoadjuvant immunochemoradiotherapy showed no significant improvement in pCR rate than NCRT (ESCC, 50% vs 48.7%, P = 0.9; EAC, 32.6% vs 23.1%, P = 0.22). Grade 3-4 AEs were the most common in patients with neoadjuvant immunochemoradiotherapy, significantly higher than immunochemotherapy (46.7% vs 32.8%, P = 0.04) and NCRT (46.7% vs 18.1%, P < 0.0001). In conclusion, for patients with resectable esophageal or GEJ carcinoma, the addition of ICIs to standard NCRT could not improve pCR rate in both ESCC and EAC, but significantly increased the risk of severe AEs. Large-scale phase 3 randomized trials were urgently needed to further confirm the survival benefit and safety profile of neoadjuvant immunotherapy.

Oesophagectomy following noncurative endoscopic resection for oesophageal carcinoma: does interval matter?

Oesophagectomy was always recommended after noncurative endoscopic resection (ER). And the optimal time interval from ER to oesophagectomy remains unclear. This study was to explore the effect of interval on pathologic stage and prognosis. We included 155 patients who underwent ER for cT1N0M0 oesophageal cancer and then received subsequent oesophagectomy from 2009 to 2019. Overall survival and disease-free survival (DFS) were analysed to find an optimal cut-off of interval from ER to oesophagectomy. In addition, pathologic stage after ER was compared to that of oesophagectomy. Logistic regression model was built to identify risk factors for pathological upstage. The greatest difference of DFS was found in the groups who underwent oesophagectomy before and after 30 days (P = 0.016). Among total 155 patients, 106 (68.39%) received oesophagectomy within 30 days, while 49 (31.61%) had interval over 30 days. Comparing the pathologic stage between ER and oesophagectomy, 26 patients had upstage and thus had worse DFS (hazard ratio = 3.780, P = 0.042). T1b invasion, lymphovascular invasion and interval >30-day group had a higher upstage rate (P = 0.014, P < 0.001 and P < 0.001, respectively). And they were independent risk factors for pathologic upstage (odds ratio = 3.782, 4.522 and 2.844, respectively). It was the first study exploring the relationship between time interval and prognosis in oesophageal cancer. The longer interval between noncurative ER and additional oesophagectomy was associated with a worse DFS, so oesophagectomy was recommended performed within 1 month after ER. Older age, T1b stage, lymphovascular invasion and interval >30 days were significantly associated with pathologic upstage, which is related to the worse outcome too.

The prognostic significance of preoperative nutritional/inflammatory markers and clinicopathological features in resectable esophagectomy patients: possibility of nutritional intervention.

Preoperative inflammatory or nutritional biomarkers and clinicopathological features may be survival predictors in resectable esophagealsquamous cell carcinoma. We included 118 patients with resectable squamous esophageal carcinoma (stages I-IV), assessing preoperative CRP- and albumin-based modified Glasgow prognostic score, the modified controlling nutritional status score, C-reactive protein, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, pathologic stage, and tumor location(s), looking for correlation with overall survival and relapse-free survival. Using univariate and Cox analysis, we selected the most reliable prognostic factors. Five-year overall survival and recurrence-free survival were 54.9% and 48.5%, respectively. C-reactive protein values correlated negatively with hypoalbuminemia (P = 0.0036). On univariate analysis, tumor stage, invasion depth, location, nodal involvement, albumin, and modified Glasgow prognostic score were significant prognostic factors for overall and recurrence-free survival. Preoperative C-reactive protein was prognostic factor for overall survival, but not for relapse-free survival (P = 0.017, 0.063, respectively). The Cox proportional hazards model showed the modified Glasgow prognostic score to be an independent prognostic factor for relapse-free survival and overall survival after using the stepwise variable selection procedure. Cox analysis including clinicopathological factors and modified Glasgow prognostic scores showed that only tumor location(s) and pathologic stage were independent prognostic factors for overall survival and recurrence-free survival. Although the modified Glasgow prognostic score is not superior to pathologic stage and tumor location as a biomarker of preoperative nutrition/inflammation and clinicopathological factors, it remains an important prognostic marker in resectable esophageal cancers. Preoperative decreased inflammatory response and improved nutritional status may contribute to prognosis in patients with esophageal cancer.

Preliminary Evaluation of Postoperative Radiotherapy between Small T-Shaped Field and All Regional Lymph Nodes Field in Thoracic Esophageal Squamous Cell Carcinoma

<h3>Purpose/Objective(s)</h3> The optimal extent of clinical target volume (CTV) for postoperative radiotherapy in complete resection thoracic esophageal squamous cell carcinoma (ESCC) patients remains controversial. This study aimed to evaluate the preliminary results of postoperative radiotherapy with standard all regional lymph nodes field and adjusted small T-shaped field. <h3>Materials/Methods</h3> A total of 75 thoracic ESCC patients were enrolled from April 2017 to March 2021, retrospectively. Among them were 63 males and 12 females, with an average age of 64.28 (range, 49-82) years. All patients received intensity-modulated radiotherapy (IMRT) at a dose of 45-50.4Gy/25-28F after radical resection of esophageal carcinoma, of which 39 cases were small T-shaped field (including bilateral supraclavicular lymph nodes, upper and middle mediastinal lymph nodes, small T group),36 cases were all regional lymph nodes field (including tumor bed, bilateral supraclavicular lymph nodes, all mediastinal lymph nodes, left gastric lymph nodes and celiac lymph nodes, control group). 24 cases (32%) received concurrent chemotherapy and 57 cases (76%) received adjuvant chemotherapy. The median follow-up period was 31(range, 15-57) months. <h3>Results</h3> At the end of follow-up period, 7 (17.9%) cases had locoregional recurrence (LRR) and 8(20.5%) had distant metastasis (DM) in small T group, while 9 (25%) cases had LRR and 9 (25%) had DM in control group. There was no significant difference in LRR rate (p=0.456) and DM rate (p=0.643) between the two groups. There was also no significant difference in the total OS rate between the two groups (p=0.146). In terms of radiotherapy parameters, in small T group, the median values of V5, V20 and average dose of the lungs were 37.31%, 16.43% and 8.11Gy, respectively. The median value of the maximum dose of spinal cord was 29.95Gy. For the heart, the median value of the average dose and V30 were 5.13Gy and 2.64%. And the median value of V40 of the stomach was 34.32%. In control group, the median values of V5, V20 and average dose of the lungs were 53.49%, 22.08% and 11.41Gy. The median value of the maximum dose of spinal cord was 36Gy. For the heart, the median value of the average dose and V30 were 27.52Gy and 37.39%. And the median value of V40 of the stomach was 63%. All of the above parameters in small T group were significantly lower than those in control group (p<0.05). In addition, we observed grade 2 radiation pneumonitis and grade 2 radiation esophagitis in both groups:9 cases of radiation pneumonia with grade 2 or above in control group and only 1 case in small T group (p<0.001). There were 15 cases of radiation esophagitis with grade 2 or above in control group and 6 cases in small T group (p=0.024). <h3>Conclusion</h3> In conclusion, radiotherapy with small T-shaped field might be a feasible and efficacious postoperative approach for ESCC patients.

124. LONGITUDINAL STUDY OF POSTOPERATIVE SYMPTOMS AND QUALITY OF LIFE IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Patients with esophageal squamous cell carcinoma have a variety of symptoms after surgery, which will affect the normal performance of various functions of patients for a long time, affect the quality of life of patients, and even affect the survival time of patients. In the past, we paid more attention to patients’ symptoms and quality of life at a single time point after surgery, which lacked continuity and long-term nature. In this study, 244 patients with esophageal squamous cell carcinoma who received thoracoscopic radical resection of esophageal carcinoma in Sichuan Tumor Hospital from April to December 2019 were selected by convenience sampling method. Adopt Chinese VERSION MD Anderson Symptom Inventory, European Organization for Research and teatment of cancer quality of life Questionnaire, EORTC QLQ-C30 and QLQ-OES18 were used to investigate the patients at 10 time points one year after surgery, and Pearson correlation analysis was used to analyze the correlation between postoperative symptoms and quality of life. Postoperative role and emotional function of the patients recovered to the baseline level 1 month after surgery, cognitive and social function recovered to the baseline level 3 months after surgery, and physical function and overall health status did not recover to the baseline level 1 year after surgery. Sleep restlessness, distress, drowsiness, and dry mouth recovered to baseline 3 months after surgery, while pain and fatigue did not recover to baseline 1 year after surgery. One year after surgery, the main symptoms were negatively correlated with body, role, emotion, cognition, social function and overall health status (P &amp;lt; 0.05). laparoscopic thoracic esophageal cancer radical surgery in patients with esophageal squamous cell carcinomas there were different degree of symptoms within one year after surgery, and multiple symptoms one year after surgery still exists, the serious influence the patient’s quality of life, health care workers should pay attention to the symptoms of patients with postoperative longitudinal change characteristic, value assessment and management of patients with symptoms, improve patient quality of life after surgery.