Standardized Management of Esophageal Fistula in Esophageal Squamous Cell Carcinoma

N/ANot Yet RecruitingNCT07353541

Peking University Cancer Hospital & Institute32 enrolled

Overview

This prospective, multi-center, observational registry study (PKU-ESCC-EF) aims to evaluate the safety and effectiveness of a standardized diagnosis and treatment protocol for esophageal fistula (EF) in patients with advanced esophageal squamous cell carcinoma (ESCC). Esophageal fistula is a severe complication that often leads to life-threatening infections and poor nutrition. This study will observe patients receiving a comprehensive management strategy, which includes fistula sealing with esophageal or airway stents, targeted anti-infective therapy, nutritional support, and subsequent systemic anti-tumor therapy. The primary goal is to assess whether this standardized approach can improve overall survival and enable more patients to receive further anti-cancer treatments.

This observational registry employs a prospective, single-arm design to recruit eligible patients with newly diagnosed esophageal fistula (tracheoesophageal or mediastinal fistula) complicating unresectable advanced esophageal squamous cell carcinoma. All enrolled participants will receive management according to a predefined standardized diagnostic and therapeutic protocol. The protocol integrates a comprehensive workflow from diagnostic assessment to multidisciplinary intervention: initial diagnosis is supported by clinical manifestations, imaging studies, and endoscopic evaluation, followed by interventional fistula closure using esophageal or airway covered stents selected according to fistula characteristics. Accompanying medical support includes anti-infective therapy, negative pressure suction, anti-reflux treatment, and nutritional support. After achieving adequate fistula control and clinical stabilization, subsequent systemic anti-tumor therapy may be administered based on investigator assessment. Prospective data collection will encompass fistula sealing status, nutritional parameters, quality of life, subsequent anti-tumor treatment rate, overall survival, and exploratory biomarker analysis of biospecimens, thereby providing real-world evidence to standardize management strategies for this serious complication.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Esophageal Squamous Cell Carcinoma (ESCC)

Interventions

Standardized Management Protocol for Esophageal FistulaOTHER

This is a comprehensive, standardized clinical management protocol for esophageal fistula in advanced esophageal squamous cell carcinoma patients. The protocol integrates multiple standardized components into a unified pathway: (1) systematic diagnosis using iodine-contrast esophagography, chest CT, and endoscopy; (2) interventional fistula sealing with covered esophageal/airway stents selected by fistula characteristics; (3) coordinated adjunctive therapy including anti-infectives, acid suppression, and negative suction; (4) mandatory nutritional assessment with early transition from parenteral to enteral feeding; and (5) a defined pathway for subsequent anti-tumor therapy after clinical recovery. This multi-modal, sequential approach differentiates it from isolated interventions by providing integrated management from diagnosis through nutritional rehabilitation to subsequent oncology care within a standardized framework.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Voluntary participation and provision of written informed consent. * Age between 18 and 75 years (inclusive). * Histologically confirmed diagnosis of esophageal squamous cell carcinoma. * Radiologically confirmed unresectable, advanced disease. * Newly diagnosed esophageal fistula (including tracheoesophageal fistula or mediastinal esophageal fistula). * Previous receipt of ≤ 3 lines of systemic anti-tumor therapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Adequate organ and marrow function within 7 days prior to potential anti-tumor treatment, as defined by: * Hemoglobin ≥ 9.0 g/dL * Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L * Platelet count ≥ 100 × 10⁹/L * Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (or ≤ 5 × ULN in the presence of liver metastases) * Serum creatinine ≤ 1.5 × ULN * Adequate cardiac, pulmonary, and renal function to be eligible for general anesthesia, with no contraindications to general anesthesia. Exclusion Criteria: * Patients with postoperative anastomotic fistula. * Uncontrolled active bleeding. * Presence of a concurrent primary malignancy other than esophageal carcinoma. * Clinically significant cardiovascular disease, including but not limited to: * Heart failure (NYHA Class III-IV) * Uncontrolled coronary artery disease, cardiomyopathy, or arrhythmia * Uncontrolled hypertension * History of myocardial infarction within the past 1 year * Neurological or psychiatric disorders that impair cognitive ability, including the presence of central nervous system metastases. * Uncontrolled, active severe clinical infection ( \> Grade 2 per NCI-CTCAE version 5.0) within 14 days prior to enrollment, including active tuberculosis (this is a contraindication for anti-tumor therapy, not for interventional procedures). * Known or self-reported HIV infection, or active Hepatitis B or Hepatitis C. * A history of interstitial lung disease (e.g., interstitial pneumonia, pulmonary fibrosis), or evidence of interstitial lung disease on baseline chest X-ray/CT.

Outcomes

Primary Outcomes

Overall Survival (OS)

Overall survival is defined as the time from the diagnosis of esophageal fistula to death from any cause

Time frame: From date of fistula diagnosis until death from any cause, assessed up to 6 months.

Secondary Outcomes

Rate of Subsequent Anti-tumor Therapy

The proportion of patients who successfully receive/re-initiate systemic anti-tumor therapy after fistula control and clinical recovery.

Time frame: From date of fistula diagnosis until the initiation of subsequent anti-tumor therapy, assessed through study completion (up to 6 months).

Fistula Sealing Success Rate

The success rate of fistula sealing, evaluated as either Complete Remission (CR) or Partial Remission (PR) according to the protocol's criteria.

Time frame: At 2 weeks and 4 weeks after the initial fistula intervention.

Nutritional Status (NRS 2002)

Nutritional risk will be assessed using the Nutritional Risk Screening 2002 (NRS 2002) tool. The total NRS 2002 score is derived from the sum of three components: Nutritional Status Impairment Score (range: 0-3 points), Disease Severity Score (range: 0-3 points), and Age Adjustment (1 point if age ≥70 years; 0 points otherwise). The total score ranges from 0 to 7 points. A higher total score indicates a greater nutritional risk (i.e., a worse outcome). In accordance with the original validation, a total score of ≥3 points is considered indicative of nutritional risk.

Time frame: From baseline through study completion (up to 6 months).

Nutritional Status (PG-SGA)

Nutritional status will be assessed using the Patient-Generated Subjective Global Assessment (PG-SGA) tool. The PG-SGA yields two primary outcomes: 1. Global Rating Categories: Patients are classified as Category A (Well nourished), Category B (Moderately malnourished or suspected of malnourishment), or Category C (Severely malnourished). 2. Total PG-SGA Score: A quantitative score is calculated from patient-generated and professional assessment components. The total score ranges from 0 to approximately 35 points. A higher score indicates a worse nutritional status and outcome (i.e., greater risk or severity of malnutrition). In clinical practice, a score of 4 or higher typically triggers the need for nutritional intervention.

Time frame: From baseline through study completion (up to 6 months).

Quality of Life (QOL)

Quality of Life will be assessed using the Functional Assessment of Cancer Therapy - Esophageal Cancer subscale (FACT-E). The FACT-E is composed of the general cancer module (FACT-G) and an esophageal cancer-specific subscale. The total score ranges from 0 to 180 points. A higher score indicates a better quality of life (i.e., a better outcome).

Time frame: From baseline through study completion (up to 6 months).

Incidence of Adverse Events (AEs)

Safety and tolerability assessed by the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE v5.0.

Time frame: From the start of the standardized management protocol until 30 days after the last intervention or through study completion, whichever comes first.

Standardized Management of Esophageal Fistula in Esophageal Squamous Cell Carcinoma

Overview

Conditions

Interventions

Eligibility

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts