Semmelweis Esophageal Cancer Study: Noninvasive Prognostic Parameters in Patients With Oesophageal and Esophagogastric Junction Cancer

Noninvasive Testing Procedures, Role of Biomarkers and Anticancer Treatments in Esophageal and Esophagogastric Cancer Survival and Quality of Life of Patients With Cancer of the Esophageopharyngeal and Oesophageophageophageal Junction

The objective of this observational study was to gain a deeper understanding of the epidemiology of the disease in Hungary through a broad analysis of patients with new-onset esophageal-oesophageal-stomach junction tumors, and to identify key parameters that could potentially influence the outcome of the disease and are closely correlated with morbidity and mortality. The investigators' primary objective is to identify potential factors and conditions that could be influenced and modified to enhance the disease outcome.

Main questions:

1. What are the measurable changes in performance, workload, nutritional status, cardiac function, mental status in the patients studied?
2. What is the time course of the changes during and after treatment?
3. Which pathological parameters are associated with disease outcome and which are potential points of intervention to improve the course of the disease?

Patients will undergo a detailed physical and nutritional assessment, non-invasive imaging tests and several questionnaires in addition to the usual pre- and post-operative examinations.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Cancer (EsC)

Detailed Description

Detailed assessment of the baseline cardiovascular risk and status (anthropometric data, physical status assessment, psychological and quality-of-life questionnaire, questionnaires on morbidity and cancer-related fatigue, 12-lead ECG, laboratory parameters, body composition, coronary CT, echocardiography and cardiac MR scan).

In addition to the conventional echocardiographic and cardiac MR parameters, the investigators also aimed to determine myocardial deformation, i.e. strain (Medis Suite QStrain) and T1 and T2 mapping values and late-type contrast enhancement and to investigate their prognostic role. To determine late-type contrast accumulation and to determine ECV (extracellular volume), patients will be given Gadovis contrast media.

At the same time as the cardiac MR scan (V0 and V4), a serum blood sample will be taken from the patients, from which the markers below will be measured. These markers are proteins or molecules that potentially play an important role in the development of tumour cachexia. The investigators aim to determine the prognostic significance of these parameters. (Myostatin, IGF-1 (Insulin-like Growth Factor 1), GDF-15 (Growth Differentiation Factor 15), IL-6 (Interleukin-6).

Patients are followed up for cardiovascular complications during anti-tumour treatment and are taken into care.

Patients will be assessed at first presentation, after neoadjuvant treatment, immediately before surgery, in the third week after surgery and in the 3rd, 6th, 9th, 12th postoperative months. Further follow-up is done by outpatient examination, by telephone or e-mail and through the eHealth system of Hungary (EESZT) until the end of the 3rd year.

Patient education:

The detailed patient information leaflet was prepared by the doctors involved in the development of the protocol at Semmelweis University.

Data storage and data protection:

Patients enrolled in the study will be given a unique identifier after enrolment. Only this unique identifier will be used in the research record, so the record will not be directly linked to the patient. No unique identifier (name, place and date of birth, clinical triage number, social security number, ID card number, etc.) will be included in the research form. A separate, locked document will be used to link the unique identifier to the patient. The system-generated unique identifier code is recorded by the clinician on paper, complete with name, social security number and patient´s social security number, prior to the first data entry. The same document contains the patient´s informed consent for the use of the data for scientific purposes. The database and the information and consent forms, including the patient´s signature, are stored by the institute coordinators.

Statistical methods:

Using TIBCO Statistica™ 13.4 software, the normality of continuous variables is tested using the Kolmogorov-Szmirnov test. A two-sample t-test is used for normal distribution assuming a two-tailed distribution and a one-tailed distribution for selected variables (Mandard Score for tumour regression). For variables with non-normal distribution, a Mann-Whitney U test is used as a non-parametric test. Long-term survival data are analysed using Kaplan-Meyer analysis and log rank test.The level of significance is set at p<0.05

Ethical requirements

The research design was drawn up in accordance with current legislation and the World Medical Assotiation´s Declaration of Helsinki.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Tamas Vass; Phone Number: +36208259039; Email: vass.tamas@semmelweis.hu

Study Locations

• Hungary
  • Budapest, Hungary
    • Recruiting
    • Semmelweis University
    • Contact: Tamas Vass; Phone Number: +36208259039; Email: vass.tamas@semmelweis.hu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with primary operable oesophageal and oesophagogastric junction tumours presenting to the upper gastrointestinal outpatient clinic at Semmelweis University.

Description

Inclusion Criteria:

• Age over 18 years
• Diagnosis of new-onset esophageal, esophagogastric junction tumor
• Elective curative surgery (open/laparoscopic regardless of surgical technique)
• Patients who have not yet received oncological treatment for their present disease

Exclusion Criteria:

• Lack of consent
• Lack of cooperation
• Contraindications for some studies: If MR scan is contraindicated, cardiac MR scan is not performed

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Postoperative length of hospital stay in days.	within 45 days
Changes in cardiac function: cardiac MR scan	Assessment of cardiac function by cardiac MR scan before starting treatment, after surgery and at postoperative month 12.	From enrollment to the 12th postoperative month
Changes in coronary status: coronary CT scan	Assessment of coronary status by coronary CT scan before starting treatment, after surgery and at postoperative month 12.	From enrollment to the 12th postoperative month
Morbidity (early and long term) classified after Clavien-Dindo.	7-day and 30-day morbidity will be detailed assessed. Grade 3 or above morbidity rate will be assessed.	30 days (until 31st postoperative day)
Early and late mortality	7-day, 30-day and 90-day mortality of each patient will be recorded	90 days (until 91st postoperative day)
Number of days spent on ICU (Intensive care unit)	Number of days observed on ICU right after operation.	within 45 days postoperative
Changes in physical performance: 6-minute walk test (6MWT)	6-minute walk test (6MWT) assessment at the first appointment, immediately before surgery, third week postoperatively and postoperative 3. 6. 9. 12. months.	From enrollment to the 12th postoperative month
Changes in physical performance: hand grip strength test	Hand grip strength test assessment at the first appointment, immediately before surgery, third week postoperatively and postoperative 3. 6. 9. 12. months.	From enrollment to the 12th postoperative month
Changes in physical performance: time up and go test	Time up and go test assessment at the first appointment, immediately before surgery, third week postoperatively and postoperative 3. 6. 9. 12. months.	From enrollment to the 12th postoperative month
Changes in ECOG (Eastern Cooperative Oncology Group) performance status	ECOG (Eastern Cooperative Oncology Group) performance status assessment at the first appointment, immediately before surgery, third week postoperatively and postoperative 3. 6. 9. 12. months.	From enrollment to the 12th postoperative month
Change in nutritional status, risk of malnutrition and nutritional ability: MUST (Malnutrition Universal Screening Tool)	Malnutrition Universal Screening Tool (MUST) score recording at the first encounter, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months. 0-2: If a patient receives a score of 0, then they are at a low risk. A patient with a score of 1 is a medium risk and any patient with a score of 2 or higher is considered high risk.	From enrollment to the 12th postoperative month
Change in nutritional status, risk of malnutrition and nutritional ability: NRS (nutritional risk score)	NRS (nutritional risk score) recording at the first encounter, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months. From enrollment to the 12th postoperative month Score 0-3: 0: absent, 3: severe	From enrollment to the 12th postoperative month
Change in nutritional status, risk of malnutrition and nutritional ability Description: PG-SGA (Patient-Generated Subjective Global Assessment)score	PG-SGA (Patient-Generated Subjective Global Assessment) score recording at the first encounter, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months. The PG-SGA allows to classify nutritional status into three categories: A= well nourished; B= suspected or moderate malnutrition; and C= severe malnutrition.	From enrollment to the 12th postoperative month
Change in nutritional status, risk of malnutrition: Bioimpedance examination	Bioimpedance examination recording at the first encounter, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months.	From enrollment to the 12th postoperative month
Change in nutritional ability: swallowing test	Swallowing test recording at the first encounter, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months.	From enrollment to the 12th postoperative month
Change in nutritional status: myostatin level	Measurement of myostatin level before the start of treatment, postoperatively and at postoperative month 12.	From enrollment to the 12th postoperative month
Change in nutritional status: IGF-1 level	Measurement of serum IGF-1 level before the start of treatment, postoperatively and at postoperative month 12.	From enrollment to the 12th postoperative month
Change in nutritional status: GDF-15 level	Measurement of serum GDF-15 level before the start of treatment, postoperatively and at postoperative month 12.	From enrollment to the 12th postoperative month
Change in nutritional status: IL-6 level	Measurement of serum IL-6 level before the start of treatment, postoperatively and at postoperative month 12.	From enrollment to the 12th postoperative month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay in beginning of adjuvant oncotherapy (chemotherapy, radiotherapy).	Sufficient recovery time until fitness of adjuvant chemo/radiotherapy will be recorded.	within 8 weeks, if adjuvant oncotherapy is needed
Change in mental status: adherence	Completion of MAS-12 (Motivation Assessment Scale) questionnaire at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months The MAS-12 total score ranges from 12 to 60 (higher score indicates higher treatment adherence)	From enrollment to the 12th postoperative month
Change in cancer related fatigue	Brief Fatigue Inventory (BFI) questionnaires at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months Scoring respondents rate each item on a 0-10 numeric scale, with 0 meaning "no fatigue" and 10 meaning "fatigue as bad as you can imagine." Scores are divided into 3 categories based on the average of each response categorized as mild (1-3), moderate (4-6), and severe (7-10).	From enrollment to the 12th postoperative month
Change in mental status: depression	Completion of PHQ-9 (Patient Health Questionnaire-9) questionnaire at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months The PHQ-9 total score ranges from 0 to 27 (scores of 5-9 are classified as mild depression; 10-14 as moderate depression; 15-19 as moderately severe depression; ≥ 20 as severe depression)	From enrollment to the 12th postoperative month
Change in mental status: anxiety	GAD-7 (General Anxiety Disorder) questionnaire at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months GAD-7 total score for the seven items ranges from 0 to 21. 0-4: minimal anxiety. 5-9: mild anxiety. 10-14: moderate anxiety. 15-21: severe anxiety.	From enrollment to the 12th postoperative month
Change in frailty: Clinical frailty scale (CFS)	Clinical frailty scale (CFS) questionnaire at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months The clinical frailty scale is a 9-point scale that quantifies frailty based on function in individual patients. It is complemented by a visual chart to assist with the classification of frailty. Higher scores indicate increased frailty and associated risks.	From enrollment to the 12th postoperative month
Change in frailty: FRAIL scale	FRAIL (Fatigue, Resistance, Ambulation, Illness, and Loss) scale questionnaire at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months The FRAIL scale includes 5 components: Fatigue, Resistance, Ambulation, Illness, and Loss of weight (10). Frail scale scores range from 0-5 (i.e., 1 point for each component; 0=best to 5=worst) and represent frail (3-5), pre-frail (1-2), and robust (0) health status.	From enrollment to the 12th postoperative month
Change in frailty: 5-item Frailty Score	5-item Frailty Score questionnaire at first appointment, immediately before surgery, third week post-operatively and post-operatively 3. 6. 9. 12. months Scored from 0 to 5 Higher number indicates higher frailty	From enrollment to the 12th postoperative month

Collaborators and Investigators

• Sponsor: Semmelweis University

Publications and helpful links

General Publications

• van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. doi: 10.1056/NEJMoa1112088.
• Lorusso A, Bichev D, Hogner A, Bartels P, Ballhausen A, Treese C, Biebl M, Thuss-Patience P. Prognostic Relevance of Weight and Weight Loss during Multimodal Therapy for Oesophagogastric Tumours. Curr Oncol. 2022 Apr 12;29(4):2706-2719. doi: 10.3390/curroncol29040221.
• Sondergaard MMA, Nordsmark M, Nielsen KM, Poulsen SH. Cardiovascular Burden and Adverse Events in Patients With Esophageal Cancer Treated With Chemoradiation for Curative Intent. JACC CardioOncol. 2021 Dec 21;3(5):711-721. doi: 10.1016/j.jaccao.2021.10.002. eCollection 2021 Dec.
• Eads JR. Cardiovascular Concerns in the Management of Esophageal Cancer Patients. JACC CardioOncol. 2021 Dec 21;3(5):722-724. doi: 10.1016/j.jaccao.2021.11.005. eCollection 2021 Dec.

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2024
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 10, 2034

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: November 27, 2024
• First Posted (Actual): December 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: frailty; heart failure; sarcopenia; malnutrition; Esophageal cancer; heart function; cardiovascular abnormalities; Esophageal cancer surgery
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Cardiovascular Diseases; Neuromuscular Manifestations; Pathologic Processes; Nutrition Disorders; Neoplasms by Site; Neoplasms; Pathological Conditions, Anatomical; Heart Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Congenital Abnormalities; Muscular Atrophy; Atrophy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Frailty; Malnutrition; Heart Failure; Esophageal Neoplasms; Sarcopenia; Cardiovascular Abnormalities
• Other Study ID Numbers: NNGYK/18646-5/2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD used in the results publication
• IPD Sharing Time Frame: Starting 6 months after publication
• IPD Sharing Access Criteria: Access to the data is available to any researcher who wishes to use the results for further research (e.g. meta-analysis, sytematic review). The request must be submitted to the research coordinator in the form of a formal e-mail. Data will be provided electronically after a data sharing agreement has been signed. The statistical methods for the analyses and the results must be approved by independent review.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No