Clinical trial NCT06713993: Semmelweis Esophageal Cancer Study: Noninvasive Prognostic Parameters in Patients With Oesophageal and Esophagogastric Junction Cancer
Official title: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Esophageal Cancer (EsC)
Keywords: Esophageal cancer
heart failure
sarcopenia
malnutrition
frailty
heart function
Esophageal cancer surgery
cardiovascular abnormalities
Lead sponsor: Semmelweis University
Sponsor class: OTHER
First posted: 2024-12-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in cardiac function: cardiac MR scan
timeFrame: From enrollment to the 12th postoperative month
measure: Changes in coronary status: coronary CT scan
timeFrame: From enrollment to the 12th postoperative month
measure: Morbidity (early and long term) classified after Clavien-Dindo.
timeFrame: 30 days (until 31st postoperative day)
measure: Early and late mortality
timeFrame: 90 days (until 91st postoperative day)
measure: Length of hospital stay
timeFrame: within 45 days
measure: Number of days spent on ICU (Intensive care unit)
timeFrame: within 45 days postoperative
measure: Changes in physical performance: 6-minute walk test (6MWT)
timeFrame: From enrollment to the 12th postoperative month
measure: Changes in physical performance: hand grip strength test
timeFrame: From enrollment to the 12th postoperative month
measure: Changes in physical performance: time up and go test
timeFrame: From enrollment to the 12th postoperative month
measure: Changes in ECOG (Eastern Cooperative Oncology Group) performance status
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status, risk of malnutrition and nutritional ability: MUST (Malnutrition Universal Screening Tool)
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status, risk of malnutrition and nutritional ability: NRS (nutritional risk score)
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status, risk of malnutrition and nutritional ability Description: PG-SGA (Patient-Generated Subjective Global Assessment)score
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status, risk of malnutrition: Bioimpedance examination
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional ability: swallowing test
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status: myostatin level
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status: IGF-1 level
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status: GDF-15 level
timeFrame: From enrollment to the 12th postoperative month
measure: Change in nutritional status: IL-6 level
timeFrame: From enrollment to the 12th postoperative month
Secondary outcomes:
measure: Change in mental status: adherence
timeFrame: From enrollment to the 12th postoperative month
measure: Change in cancer related fatigue
timeFrame: From enrollment to the 12th postoperative month
measure: Delay in beginning of adjuvant oncotherapy (chemotherapy, radiotherapy).
timeFrame: within 8 weeks, if adjuvant oncotherapy is needed
measure: Change in mental status: depression
timeFrame: From enrollment to the 12th postoperative month
measure: Change in mental status: anxiety
timeFrame: From enrollment to the 12th postoperative month
measure: Change in frailty: Clinical frailty scale (CFS)
timeFrame: From enrollment to the 12th postoperative month
measure: Change in frailty: FRAIL scale
timeFrame: From enrollment to the 12th postoperative month
measure: Change in frailty: 5-item Frailty Score
timeFrame: From enrollment to the 12th postoperative month
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Semmelweis University
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.