Metastatic Esophageal Cancer Research Articles

Characterization of the fecal microbiota in gastrointestinal cancer patients and healthy people.

The incidence and mortality of gastrointestinal (GI) tumors are high in China. Some studies suggest that the gut microbiota is related to the occurrence and development of tumors. At present, there are no prospective studies based on the correlation between gastrointestinal tumors and gut microbiota in the Chinese population. The objective of this report is to characterize the fecal microbiota in healthy control participants and patients with esophageal cancer, gastric cancer, and colorectal cancer. Patients with locally advanced or metastatic esophageal, gastric, and colorectal cancer were enrolled, and healthy people were included as controls. 16S rRNA sequencing was used to analyze the characteristics of fecal microbiota. PICRUSt software was used for functional prediction. Significant differences in the composition and abundance of fecal microbiota were identified between gastrointestinal cancer patients (n = 130) and healthy controls (n = 147). The abundance of Faecalibacterium prausnitzii, Clostridium clostridioforme and Bifidobacterium adolescent in tumor groups were all significantly lower than in the control group (P < 0.05). The levels of Blautia producta and R. faecis in the gastric (n = 46) and colorectal cancer (n = 44) groups were significantly lower than those in the control group (P < 0.05). The level of Butyricicoccus pullicaecorum in the esophageal cancer (n = 40) and gastric cancer groups was significantly lower than that in the control group (P < 0.05). B. fragilis, Akkermansia muciniphila, Clostridium hathewayi and Alistipes finegoldii were overabundant in the different tumor groups compared with the control (P < 0.05). We observed significant differences in functional metabolism and cell biological function between the tumor and control groups (P < 0.05). Optimal microbial markers were identified on a random forest model and achieved an area under the curve of 85.59% between 130 GI cancer samples and 147 control samples. The respective AUC values were 86.89%, 97.11%, and 79.1% in detecting esophageal cancer, gastric cancer, and colorectal cancer. Patients with esophageal or gastric cancers had similar features of fecal bacteria as those with colorectal cancer. The metabolic function of fecal bacteria in the gastrointestinal cancer patients and the healthy controls were different. The microbial signatures may potentially be applied to distinguish GI cancer patients from healthy people as a non-invasive diagnostic biomarker.

Beyond median overall survival: Estimating multiple survival scenarios in patients with metastatic esophagogastric cancer.

261 Background: Recent clinical trials of novel systemic therapies showed improved survival of patients with metastatic esophageal cancer (EC) and gastric cancer (GC). Survival improvements observed in clinical trials might be unrepresentative for the total population as the percentage of patients whom participate in clinical trials is limited and more than half of all patients receive best supportive care (BSC). The aim of our study is to assess the best-case, typical and worst-case survival scenarios in patients with metastatic esophagogastric cancer. Methods: We selected patients with metastatic EC (including junction) or GC diagnosed in 2006-2019 from the Netherlands Cancer Registry. Survival scenarios were calculated based on percentiles of the survival curve stratified by tumor location and treatment (tumor-directed therapy or BSC). Survival scenarios were calculated for the 10th (best-case), 25th (upper-typical), 75th (lower-typical) and 90th (worst-case) percentiles. Linear trend analysis was performed to test if changes in survival over the diagnosis years were significant. Results: We identified 12739 patients with EC and 6833 patients with GC. Percentage of patients receiving tumor-directed therapy increased from 34% to 47% and 30% to 45% for patients with EC and GC, respectively. The median survival remained unchanged for patients with EC (5.0 months) and improved slightly for patients with GC (3.1 to 3.7 months; P=0.006). For patients with EC survival of the best-case scenario improved (17.4 to 22.8 months; P=0.001), whereas the other scenarios remained unchanged: upper-typical 11.2 to 11.7 (P=0.11), lower-typical 2.1 to 2.0 (P=0.10) and worst-case 0.9 to 0.8 months (P=0.22). For patients with GC survival improved for the best-case (13.1 to 19.5; P=0.005) and upper-typical scenario (6.7 to 10.6 months; P=0.002), whereas the lower-typical (1.2 to 1.4 months; P=0.87) and worst-case (0.6 to 0.6 months; P=0.60) remained unchanged. For patients with EC receiving tumor-directed therapy survival in all scenarios remained unchanged while for patients receiving BSC survival decreased: best-case 11.8 to 9.8 (P=0.005), upper-typical 6.0 to 5.0 (P=0.002), lower-typical 1.4 to 1.0 (P=0.003) and worst-case 0.7 to 0.5 months (P=0.03). For patients with GC receiving tumor-directed therapy survival improved for all scenarios: best-case 19.8 to 30.4 (P=0.005), upper-typical 6.4 to 10.3 (P=0.002), lower-typical 3.6 to 5.4 (P&lt;0.001) and worst-case 1.4 to 2.6 months (P&lt;0.001), and for patients receiving BSC survival for all scenarios remained unchanged. Conclusions: The proportion of patients with EC and GC receiving tumor-directed therapy increased over time. Despite the fact that survival improvements were not observed across all scenarios, at least an increase in survival was observed in certain subgroups of patients.

Use of Palliative Care Among Commercially Insured Patients With Metastatic Cancer Between 2001 and 2016.

Early palliative care, concomitant with disease-directed treatments, is recommended for all patients with advanced cancer. This study assesses population-level trends in palliative care use among a large cohort of commercially insured patients with metastatic cancer, applying an expanded definition of palliative care services based on claims data. Using nationally representative commercial insurance claims data, we identified patients with metastatic breast, colorectal, lung, bronchus, trachea, ovarian, esophageal, pancreatic, and liver cancers and melanoma between 2001 and 2016. We assessed the annual proportions of these patients who received services specified as, or indicative of, palliative care. Using Cox proportional hazard models, we assessed whether the time from diagnosis of metastatic cancer to first encounter of palliative care differed by demographic characteristics, socioeconomic factors, or region. In 2016, 36% of patients with very poor prognosis cancers received a service specified as, or indicative of, palliative care versus 18% of those with poor prognosis cancers. Being diagnosed in more recent years (2009-2016 v 2001-2008: hazard ratio [HR], 1.8; P < .001); a diagnosis of metastatic esophagus, liver, lung, or pancreatic cancer, or melanoma (v breast cancer, eg, esophagus HR, 1.89; P < .001); a greater number of comorbidities (American Hospital Formulary Service classes > 10 v 0: HR, 1.71; P < .001); and living in the Northeast (HR, 1.43; P < .001) or Midwest (v South: HR, 1.39; P < .001) were the strongest predictors of shorter time from diagnosis to palliative care. Use of palliative care among commercially insured patients with advanced cancers has increased since 2001. However, even with an expanded definition of services specified as, or indicative of, palliative care, < 40% of patients with advanced cancers received palliative care in 2016.

POSB171 Using French Administrative Database to Identify Patients with Unresectable/Locally Advanced or Metastatic Esophageal Cancer in France

POSB171 Using French Administrative Database to Identify Patients with Unresectable/Locally Advanced or Metastatic Esophageal Cancer in France

POSB47 Hospital Management and Costs of Unresectable/Locally Advanced or Metastatic Esophageal Cancer in France (Occasion Study)

POSB47 Hospital Management and Costs of Unresectable/Locally Advanced or Metastatic Esophageal Cancer in France (Occasion Study)

Can we do without chemotherapy? A perspective on the combinations nivolumab-chemotherapy and nivolumab–ipilimumab in metastatic gastric and esophageal cancer

Can we do without chemotherapy? A perspective on the combinations nivolumab-chemotherapy and nivolumab–ipilimumab in metastatic gastric and esophageal cancer

Effect and safety of anlotinib combined with S-1 for recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy.

This study aimed to evaluate the effect and safety of anlotinib combined with S-1 in the treatment of recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy.This study retrospectively reviewed 22 recurrent or metastatic esophageal cancer patients who refused or were intolerant to intravenous chemotherapy between June 1, 2018 and February 28, 2019. All patients did not previously receive anlotinib or S-1.Of 22 patients, 20 patients had squamous cell cancer. Seventeen patients received at least 2 cycles of anlotinib plus S-1. The objective response rate (ORR) was 35.3%, and the disease control rate (DCR) was 82.4%. The median progression-free survival (PFS) was 3.5 months, and median overall survival (OS) was 5.2 months. In the first-line treatment subgroup, the ORR was 50%, the DCR was 80%, the median PFS was 4.5 months, and the median OS was 5.8 months. In the second-line and above treatment subgroup, the ORR was 14.3%, the DCR was 85.7%, the median PFS was 3.0 months, and the median OS was 3.7 months. The main adverse events (AEs) of anlotinib combined with S-1 were fatigue (58.8%), hypertension (47.1%), hemoptysis (29.4%), anemia (29.4%), nausea (23.5%), liver function damage (23.5%), albuminuria (17.6%), abdominal pain (17.6%), leukopenia (17.6%), neutropenia (11.8%), fever (11.8%), and hand-foot syndrome (11.8%). Grade 3 AEs included nausea (5.9%) and hypertension (5.9%), and no grade 4 or more AEs were reported.Anlotinib combined with S-1 achieved promising disease control and satisfactory survival with tolerable safety in recurrent metastatic esophageal cancer who refused or were intolerant to intravenous chemotherapy.

The Relationship Between Gut Microbiome Features and Chemotherapy Response in Gastrointestinal Cancer.

ObjectiveThe prognosis of advanced gastrointestinal cancer is poor. There are studies indicating that gut microbes might have the predictive ability to evaluate the outcome of cancer therapy, especially immunotherapy. There is limited evidence to date on the influence of microbes on chemotherapeutic response.DesignIn total, 130 patients with advanced or metastatic esophageal (n=40), gastric (n=46), and colorectal cancer (n=44) were enrolled. We included 147 healthy people as controls and used 16S rRNA sequencing to analyze the fecal microbiota.ResultsSignificant differences in the abundance of fecal microbiota between patients with gastrointestinal cancer and controls were identified. The abundance of Bacteroides fragilis, Escherichia coli, Akkermansia muciniphila, Clostridium hathewayi, and Alistipes finegoldii were significantly increased in the patient group. Faecalibacterium prausnitzii, Roseburia faecis, Clostridium clostridioforme, Blautia producta, Bifidobacterium adolescent, and Butyricicoccus pullicaecorum taxa were significantly more abundant in the controls. The amount of R. faecis in non-responders (NR) was more likely to decrease significantly after chemotherapy, while the amount mostly increased in responders (R) (P=0.040). The optimal abundance variation of R. faecis may be a predictor for distinguishing patients with PD from those with non-PD in all patients with gastrointestinal cancer, with a sensitivity of 75.0% and a specificity of 93.9%.ConclusionThe gut microbiome of patients with esophageal cancer, gastric cancer, and colorectal cancer differs from those of healthy people. The abundance alteration of R. faecis in patients with GI cancer might be a predictor of chemotherapy efficacy.

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study

Background: Oesophageal cancer comprises 2 different histological variants: oesophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC). While there are multiple therapeutic options for both types, patients with advanced or metastatic oesophageal cancer still suffer from poor prognosis. Aims: The study aimed to examine the association between the risk of oesophageal cancer and medications and to estimate the chemopreventive effects of commonly used drugs. Methods: A multicentre retrospective cohort study was conducted using data from 9 hospital databases of hospitalized patients between 2014 and 2019. The primary outcomes were ESCC and EAC. The association of oesophageal cancer with drug use and clinical factors was evaluated. Odds ratios (ORs) were adjusted for age, sex, Charlson comorbidity index scores, and smoking with/without gastro-oesophageal reflux disease. Results: The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, p < 0.0001), aspirin (aOR 0.32, p < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, p = 0.0005), steroid (aOR 0.19, p < 0.0001), statin (aOR 0.43, p < 0.0001), and metformin (aOR 0.42, p < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, p = 0.0006) and steroids (aOR 0.54, p = 0.022) was associated with a lower risk of EAC than that in non-use. Conclusion: COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

Pembrolizumab (Keytruda)

&#x0D; CADTH recommends that Keytruda should be reimbursed by public drug plans for the treatment of esophageal or human epidermal growth factor receptor 2 (HER2)-negative esophagogastric junction (EGJ) cancer that cannot be removed by surgery or is metastatic, if certain conditions are met.&#x0D; Keytruda should only be covered to treat adult patients who have not received previous treatment for advanced or metastatic esophageal or EGJ cancer and who have good performance status.&#x0D; Keytruda should only be reimbursed if prescribed in combination with platinum and fluoropyrimidine–based chemotherapy and given by a clinician who is experienced in treating cancer. The price of Keytruda must be lowered to be cost-effective and affordable.&#x0D;

O-OGC09 PD-1 inhibitors in Oesophageal Cancer: A systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic landscape

Abstract Background Patients with oesophageal or gastro-oesophageal junction (GOJ) cancer that fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors have emerged as exciting therapeutic options in other solid tumors, such as non-small cell lung cancer, renal cell carcinoma and melanoma. We assessed the efficacy and safety of PD-1 inhibitors in oesophageal and GOJ cancers. Methods This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE and Google Scholar databases was conducted up to April 1st 2021. Results This review identified nine eligible studies reporting outcomes of 2149 patients treated with PD-1 blockade compared with 1244 patients treated with either a placebo or the standard regimen of chemotherapy for oesophageal and GOJ cancer. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic oesophageal and GOJ cancer while maintaining acceptable safety profiles. Promising survival data has also recently emerged from PD-1 blockade in the adjuvant setting. Conclusions PD-1 blockade in oesophageal and GOJ cancer has delivered impressive survival benefit whilst remaining well tolerated. Its use in the adjuvant setting may further advance our treatment options for this difficult-to-treat tumour, and more advancements in the immunotherapy landscape are highly anticipated. However, further characterization of the PD-1/PD-L1 pathway is required to optimise patient selection.

Role of surgery in the management of synchronous metastatic esophageal cancer

Role of surgery in the management of synchronous metastatic esophageal cancer

Role of surgery in the management of synchronous metastatic esophageal cancer

Role of surgery in the management of synchronous metastatic esophageal cancer

КЛИНИЧЕСКИЙ СЛУЧАЙ ЛЕЧЕНИЯ РАКА ПИЩЕВОДА IV СТАДИИ

In 2018 in Russian Federation more than 500 thousand new cases of cancer were found, including 8000 cases with malignant tumors of esophagus and more than 30 % of patients have the IV stage.&#x0D; Esophageal cancer takes the 6-th place in death causes connected to cancer in the world and it is still one of the main global problems in medical care. Oncologists face the problem of the most difficult choice in treatment tactics for spread stages of disease. In this situation it is recommended to provide combined treatment (surgery, neoadjuvant and adjuvant chemotherapy). &#x0D; Definitive radiotherapy or chemoradiotherapy (without surgery) is used for patients with unrespectable esophageal tumor. &#x0D; In this article we present clinical case of successful treatment of a patient with metastatic esophageal cancer. The patient got chemoradiotherapy in 2017 and after control checkup in November 2019 remission was registered. After provided treatment stopping of pain syndrome and dysphagia, food passage through esophagus was restored. The patient notes good life quality, he is physically active and socially adapted.

HYPOTHYROIDISM GONE AWRY: A CASE OF MYXEDEMA COMA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Myxedema coma (MC) is a severe form of hypothyroidism and considered a medical emergency. It is characterized by decreased mentation, bradycardia, depressed respiratory status, hypotension, and general slowing of bodily systems. This a rare condition usually induced by stressors such as infection or malignancy. Here we present a patient undergoing treatment for metastatic carcinoma with incidental diagnosis of this aggressive endocrinological emergency. CASE PRESENTATION: 45-year-old Chinese gentleman with a 2-year history of metastatic esophageal cancer who presented unresponsive. He was undergoing palliative treatment, residing in a nursing home. On admission he required intubation and was found to have mets to his brain which can induce seizures, and was thought to be the cause of his unresponsiveness. He was hypotensive, hyponatremic, minimally responsive, with a lower respiratory rate on arrival. These features fit hypothyroidism. He was started on Dexamethasone for possible vasogenic edema from the brain mets. Lab work discovered TSH to be 162.4 with a FT4 of 0.27. Labs also discovered evidence of adrenal insufficiency with AM cortisol being low despite two days of high dose steroids. He received IV levothyroxine and Stress dose Hydrocortisone. DISCUSSION: : Our patient may have had many precipitating factors of his MC. He had a history of undergoing chemo-radiation before transitioning to palliative care in light of his aggressive cancer. He was receiving PEG tube feeds for over a year which may have impaired metabolism of his levothyroxine. He also continued to lose weight due to his malignancy, without proper readjustment in his weight-based medications. His chronic malnourished state may have contributed to refractory hypothyroidism precipitating MC. CONCLUSIONS: The mortality rates for myxedema coma can range between 30-50% based on different studies. In patients who are terminal, such as our patient with metastatic carcinoma, it is still prudent to keep in mind a simple chronic underlying condition such as hypothyroidism should not go unchecked. Fatal consequences may ensue if thyroid levels are not routinely checked in such individuals. REFERENCE #1: Acharya, R., Cheng, C., Bourgeois, M., Masoud, J., & McCray, E. (2020, September 16). Myxedema Coma: A forgotten medical emergency with a PRECIPITOUS ONSET. Retrieved February 10, 2021, from https://www.cureus.com/articles/41411-myxedema-coma-a-forgotten-medical-emergency-with-a-precipitous-onset REFERENCE #2: Aksoy, N., & Odabasi, G. (n.d.). 23 - case REPORT: Myxedema coma as a complication of cancer treatments. Retrieved February 10, 2021, from https://www.morressier.com/article/23--case-report-myxedema-coma-complication-cancer-treatments/5cdbe0a6618793e647b11e09 REFERENCE #3: Gummalla, S., Manjunath, M., & Phillips, B. (2020, October 22). Myxedema Coma: A life-threatening condition in patients USING PEMBROLIZUMAB. Retrieved February 10, 2021, from https://www.hindawi.com/journals/crie/2020/8855943/ DISCLOSURES: No relevant relationships by Padmini Giri, source=Web Response No relevant relationships by Victoria Gonzalez, source=Web Response No relevant relationships by Zain Kulairi, source=Web Response No relevant relationships by Sourabh Sourabh, source=Web Response No relevant relationships by DANYAL TAHERI ABKOUH, source=Web Response

Second-line pembrolizumab versus chemotherapy in Japanese patients with advanced esophageal cancer: subgroup analysis from KEYNOTE-181

BackgroundSafe and effective treatments for advanced esophageal cancer are an unmet need in Japan. We report results of a subgroup analysis of Japanese patients enrolled in KEYNOTE-181, a randomized, open-label, phase 3 study of pembrolizumab versus chemotherapy as second-line therapy for patients with advanced or metastatic esophageal cancer whose disease progressed after standard first-line therapy.MethodsPatients were randomly assigned 1:1 to receive pembrolizumab 200 mg every 3 weeks or investigator’s choice of paclitaxel, docetaxel, or irinotecan. Efficacy was evaluated in all Japanese patients and in those with programmed death ligand 1 combined positive score ≥ 10.ResultsOf the 152 Japanese patients enrolled (pembrolizumab, n = 77; chemotherapy, n = 75), 150 (98.7%) had squamous cell carcinoma and 79 (52.0%) had combined positive score ≥ 10. At the final analysis, median overall survival was improved among all patients (12.4 vs 8.2 months with pembrolizumab and chemotherapy, respectively; hazard ratio, 0.68; 95% CI 0.48–0.97) and patients with combined positive score ≥ 10 (12.6 vs 8.4 months; hazard ratio, 0.68; 95% CI 0.42–1.10). Fewer patients had any-grade (74.0% vs 95.9%) or grade 3–5 (16.9 vs 50.0%) treatment-related adverse events with pembrolizumab than with chemotherapy.ConclusionConsistent with the global trial results, second-line pembrolizumab therapy showed a survival benefit and a favorable safety profile compared with chemotherapy in Japanese patients with advanced esophageal cancer.

The risk and prognostic factors for brain metastases in esophageal cancer patients: an analysis of the SEER database

BackgroundBrain metastases were rare in esophageal cancer patients. Using the Surveillance, Epidemiology, and End Results (SEER) database, the present study investigated the incidence, risk and prognostic factors of brain metastases in esophageal cancer patients.MethodsRetrieving esophageal cancer patients diagnosed between 2010 and 2018 from the SEER database, univariable and multivariable logistic and cox regression models were used to investigate the risk factors for brain metastases development and prognosis, respectively. The brain metastases predicting nomogram was constructed, evaluated and validated. The overall survival (OS) of patients with brain metastases was analyzed by Kaplan–Meier method.ResultsA total of 34,107 eligible esophageal cancer patients were included and 618 of them were diagnosed with brain metastases (1.8%). The median survival of the brain metastatic esophageal cancer patients was 5 (95% CI: 5–7) months. The presence of bone metastases and lung metastases were the homogeneously associated factors for the development and prognosis of brain metastases in esophageal cancer patients. Patients younger than 65 years, American Indian/Alaska Native race (vs. White), overlapping lesion (vs. Upper third), esophageal adenocarcinoma histology subtype, higher N stage, and liver metastases were positively associated with brain metastases occurrence. The calibration curve, ROC curve, and C-index exhibited good performance of the nomogram for predicting brain metastases.ConclusionsHomogeneous and heterogeneous factors were found for the development and prognosis of brain metastases in esophageal cancer patients. The nomogram had good calibration and discrimination for predicting brain metastases.

Camrelizumab plus Chemotherapy for Metastatic Esophageal Squamous Cell Cancer

The immune checkpoint inhibitor pembrolizumab combined with chemotherapy was recently approved by the FDA for first-line treatment of esophageal and

PD-1 inhibitors in esophageal cancer: a systematic review of the oncological outcomes associated with PD-1 blockade and the evolving therapeutic paradigm.

Patients with esophageal or gastroesophageal junction (GEJ) cancer who fail to respond to chemoradiotherapy have a poor clinical prognosis. Recent clinical trials have investigated the use of immune checkpoint inhibitors in these patients. The use of programmed cell death protein 1 (PD-1) inhibitors has emerged as exciting therapeutic options in the curative and palliative setting of other solid tumors. We assessed the efficacy and safety of PD-1 inhibitors in esophageal and GEJ cancers. This systematic review was performed in accordance with the PRISMA guidelines. A comprehensive electronic literature search from the EMBASE, Pubmed, Scopus, MEDLINE, and Google Scholar databases was conducted up to 25 July 2021. This review identified 11 eligible studies reporting outcomes of 3451 patients treated with PD-1 blockade compared with 2286 patients treated with either a placebo or the standard regimen of chemotherapy. Clinically significant improvements in median overall survival have been demonstrated in advanced and metastatic esophageal and GEJ cancer while maintaining acceptable safety profiles. Promising survival data have also recently emerged from PD-1 blockade in the adjuvant setting. PD-1 blockade in esophageal and GEJ cancer has delivered impressive survival benefit while remaining well tolerated. Its use in the adjuvant setting will further advance treatment options, and more advancements in this area of therapy are highly anticipated. However, further characterization of the PD-1/programmed death ligand-1 pathway and elucidation of biomarkers to predict response are required to optimize patient selection.

LBA52 Sintilimab plus chemotherapy versus chemotherapy as first-line therapy in patients with advanced or metastatic esophageal squamous cell cancer: First results of the phase III ORIENT-15 study

ORIENT-15 is a global, randomized, double-blind study to evaluate the efficacy and safety of sintilimab + chemo (S+C) vs chemo (C) as first-line (1L) treatment in patients (pts) with unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).