Gastric Cancer, Gastroesophageal Junction Cancer, Locally Advanced Esophageal Cancer
Conditions
Keywords
autonomic nervous system, physiotherapy, gastric cancer, nutritional intervention, psychologic support, esophageal cancer
Brief summary
Perioperative chemotherapy (CHT) or CHT/RT combined with surgery is the standard therapeutic approach for the treatment of locally advanced cancer of the esophagus, gastroesophageal junction (GEJ), and stomach. Comprehensive cancer treatment is associated with high perioperative morbidity and mortality. Serious postoperative complications occur in up to 20-80% of patients undergoing esophagectomy. The impact of nutritional status and overall physical condition on surgical outcomes and overall treatment has been demonstrated many times. The concept of pre-rehabilitation/pre-optimization, which involves establishing an individualized nutritional plan, monitoring and managing physical activity, and providing comprehensive supportive oncological and psychological care as early as during neoadjuvant CHT or CHT/RT, is a prerequisite for improving perioperative and 30-day postoperative morbidity and mortality.
Detailed description
Standard care for locally advanced diseases includes perioperative chemotherapy or preoperative chemoradiotherapy, which can, in turn, lead to patient deconditioning prior to surgery. Efforts to overcome these complications led to the development of the ERAS (Enhanced Recovery After Surgery) program. This program overlaps with the emerging concept of prehabilitation/pre-optimization, which is based on identifying risk factors, formulating nutritional support, creating an exercise plan to improve overall physical fitness, and implementing continuous psychological support to enhance the patient's postoperative recovery. The autonomic nervous system (ANS) is the body's primary homeostatic regulatory system, which can be negatively affected by anticancer treatment. Heart rate variability (HRV) is a suitable candidate for monitoring ANS function and can provide early indication of a deterioration in the sympathovagal balance of test subjects. As mentioned above, preoperative chemotherapy may further affect ANS function. It is known that regimens based on oxaliplatin and paclitaxel cause peripheral neuropathy and are associated with a significant impact on the adrenergic cardiovascular response and parasympathetic cardiac innervation. We hypothesize that a controlled increase in physical cardiorespiratory fitness during the preoperative period could improve HRV and aerobic performance, taking into account the patient's current condition. An integral part of a comprehensive program should also be perioperative individualized nutritional support aimed at maintaining body weight and muscle mass. The most common adverse effects of cancer treatment include cardiac toxicity, peripheral neuropathy, cachexia, loss of appetite, cognitive changes, fatigue, nausea, pain, and sleep disturbances, which have a significant impact on patients' quality of life. For this reason, special attention must also be paid to psychological support during active cancer treatment and in follow-up care. Psychological assessment should serve as a long-term tool for patients and families both during and after the active treatment course. Considering all the above aspects, a comprehensive assessment prior to treatment initiation and a specialized comprehensive program should be approached as a prehabilitation process. Furthermore, this concept, together with ERAS and six-month postoperative follow-up, constitutes optimal management of patients with esophageal cancer.
Interventions
DIAGNOSTIC_TESTCardiorespiratory fitness (FsPS)
A single measurement before the start of preoperative treatment (baseline), after completion of chemotherapy 4-2 weeks before surgery, and 6 months after surgery.
OTHERExercises you can do on your own at home
Exercise training is prescribed in accordance with the guidelines for prescribing physical activity (the FITT methodology published by the ACSM in 2018) for a period of 2 months. Training is set at 60% of the baseline maximum inspiratory pressure (MIP) and is increased by 5% if the participant reports a rate of perceived exertion (RPE) \< 7 (RPE scale 1-10). Exercises is conducted under supervision using telemedicine technologies. Weekly online check-ins via video call using the MOU MEDDI platform (first 4 weeks), then once every 14 days. Alternatively, weekly training sessions at the gym for the first 4 weeks (3 times a week at home, walking for at least 30 minutes per training session), followed by independent training at home. The intensity of aerobic training is prescribed based on a target heart rate of 60-80% of the heart rate reserve. An important part of the evaluation is also the patient's adherence to the exercise intervention and their level of physical activity.
OTHEREnhanced Recovery After Surgery ERAS
1. Preoperative evaluation in the Anesthesiology and Resuscitation Department (ARD)/Intensive Care Unit (ICU) and preoperative intensive care, assessment of the patient's condition, development of an anesthetic plan, and consultation with the patient and their family members. 2. Application of ERAS principles in the immediate preoperative period. 3. Application of ERAS principles intraoperatively. 4. Application of ERAS principles for the postoperative period. 5. Implementation of early detection of complications and their immediate resolution.
OTHERNutritional support
1. Assessment of nutrition using the SGA (Seven-Point Subjective Global Assessment) 2. Assessment of nutritional status (nutritional requirements) using laboratory values, anthropometry, and bioimpedance 3. Assessment of weight loss or gain using selected parameters 4. Assessment of intake of regular food, oral dietary supplements, dietary modifications, and artificial nutrition
OTHERPsychological support
Psychological intervention is provided to each patient at the following time points: 1) upon enrollment in the study, 2) before surgery, 3) 30 days after surgery, and 4) 6 months after surgery.
OTHERQuality of life
It is assessed using standardized questionnaires.
DIAGNOSTIC_TESTLaboratory tests
Monitoring of cellular and humoral immunity/endocrine function will be performed by flow cytometry using two peripheral blood samples (1 tube containing 2.7 mL of EDTA-anticoagulated blood and 1 tube containing 5 mL of anticoagulant-free blood for serum separation) at 4 time points: 1) upon study enrollment, 2) before surgery, 3) 30 days after surgery, and 4) 6 months after surgery. Multicolor (6 to 8 colors) protocols for the proposed immune profile have already been established.
Sponsors
Masaryk Memorial Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
PRESCREENING STAGING VISIT 1 (0-6 weeks before neoadjuvant therapy ± 7 days) NEOADJUVANT THERAPY (8-10 weeks before surgery ± 7 days) RE-STAGING VISIT 2 (2-4 weeks before surgery ± 7 days) VISIT 2a (max. one week before surgery) SURGERY (+ ERAS) VISIT 3 (30 days after surgery +/- 7 days) VISIT 4 (6 months after surgery +/- 4 weeks)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consent to participate in the study * Age ≥ 18 years * Patients with locally advanced esophageal or gastric cancer indicated for comprehensive perioperative treatment * Resectable disease * ECOG performance status 0-2 * Ability to participate in a fitness program * Willingness to follow a nutritional plan and recommendations
Exclusion criteria
* Disseminated disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Autonomic Nervous System Balance as Measured by Heart Rate Variability | Baseline (pre-intervention), Perioperative, 1 year | Evaluation of the root mean square of successive differences in milliseconds between heartbeats to assess parasympathetic activity. |
| Change From Baseline in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index | Baseline (pre-intervention), Perioperative, 1 year | Total score on the Pittsburgh Sleep Quality Index questionnaire (range 0-21), where higher scores indicate poorer sleep quality |
| Change From Baseline in Health-Related Quality of Life as Measured by the EORTC QLQ-C30 Questionnaire | Baseline (pre-intervention), Perioperative, 1 year | Global health status/Quality of life scale score (range 0-100) from the European Organisation for Research and Treatment of Cancer core questionnaire |
| Change From Baseline in Fatigue Severity as Measured by the Functional Assessment of Chronic Illness Therapy - Fatigue Scale | Baseline (pre-intervention), Perioperative, 1 year | Total score on the 13-item fatigue subscale (range 0-52), where lower scores indicate higher levels of fatigue. |
| Change From Baseline in Cardiorespiratory Fitness as Measured by Peak Oxygen Consumption (VO2 peak) | Baseline (pre-intervention), 1 year | Peak oxygen uptake measured in ml/kg/min during a cardiopulmonary exercise test on a cycle ergometer. |
| Change From Baseline in Muscle Strength as Measured by Handgrip Dynamometry | Baseline (pre-intervention), Perioperative, 1 year | Maximum grip strength measured in kilograms (kg) using a calibrated handheld dynamometer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Postoperative Respiratory Complications | Perioperative | Percentage of participants experiencing respiratory complications (e.g., pneumonia, respiratory failure) as defined by the Clavien-Dindo classification (Grade II or higher). |
| Incidence of Anastomotic Dehiscence | Perioperative | Percentage of participants with radiologically or clinically confirmed leakage at the site of surgical anastomosis. |
| Change From Baseline in Daily Physical Activity Level as Measured by Average Daily Step Count | Baseline (pre-intervention), Perioperative, 1 year | Average number of steps per day recorded by a digital pedometer/accelerometer. |
| Change From Baseline in Lean Body Mass as Measured by Bioelectrical Impedance Analysis | Baseline (pre-intervention), Perioperative, 1 year | Total lean body mass measured in kilograms (kg) using a multi-frequency Bioelectrical Impedance Analysis device. |
| Change From Baseline in Nutritional Intake (Protein Intake) | Baseline (pre-intervention), Perioperative, 1 year | Daily protein intake measured in grams per kilogram of body weight (g/kg/day) based on a 3-day food record. |
| Change From Baseline in Psychological Distress as Measured by the Hospital Anxiety and Depression Scale | Baseline (pre-intervention), Perioperative, 1 year | Total score for anxiety and depression subscales (each range 0-21) to evaluate the impact of psychological support. |
Countries
Czechia
Contacts
CONTACTMartina Lojová, PhD
CONTACTTereza Štěpánková, PhD
PRINCIPAL_INVESTIGATORRadka Lordick Obermannová, Doc, MD, PhD
Masaryk Memorial Cancer Institute
Outcome results
None listed