Comprehensive Perioperative Program Based on Prehabilitation, Nutritional Intervention and Psychological Support for Patients With Locally Advanced Operable Oesophagogastric Cancer

Official title

A Comprehensive Preoperative and Postoperative Program Consisting Of Active Physical Therapy, A Comprehensive Nutritional Plan, And Psychological Support For Patients With Locally Advanced, Resectable Cancer Of The Esophagus, Gastroesophageal Junction, and Stomach

Overview

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 test Cardiorespiratory 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.
• Other Exercises 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 platfo
• Other Enhanced 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 detectio
• Other Nutritional 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
• Other Psychological 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.
• Other Quality of life
  It is assessed using standardized questionnaires.
• Diagnostic test Laboratory 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.

Primary outcome measures

• Change From Baseline in Autonomic Nervous System Balance as Measured by Heart Rate Variability [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Health-Related Quality of Life as Measured by the EORTC QLQ-C30 Questionnaire [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Fatigue Severity as Measured by the Functional Assessment of Chronic Illness Therapy - Fatigue Scale [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Cardiorespiratory Fitness as Measured by Peak Oxygen Consumption (VO2 peak) [Time frame: Baseline (pre-intervention), 1 year]
• Change From Baseline in Muscle Strength as Measured by Handgrip Dynamometry [Time frame: Baseline (pre-intervention), Perioperative, 1 year]

Secondary outcome measures (6)

• Incidence of Postoperative Respiratory Complications [Time frame: Perioperative]
• Incidence of Anastomotic Dehiscence [Time frame: Perioperative]
• Change From Baseline in Daily Physical Activity Level as Measured by Average Daily Step Count [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Lean Body Mass as Measured by Bioelectrical Impedance Analysis [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Nutritional Intake (Protein Intake) [Time frame: Baseline (pre-intervention), Perioperative, 1 year]
• Change From Baseline in Psychological Distress as Measured by the Hospital Anxiety and Depression Scale [Time frame: Baseline (pre-intervention), Perioperative, 1 year]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Supportive care

Study locations

Czechia · 1 center

• Masaryk Memorial Cancer Institute — Brno

Publications

• https://doi.org/10.1007/PL00007853
• Kawata S, Hiramatsu Y, Shirai Y, Watanabe K, Nagafusa T, Matsumoto T, Kikuchi H, Kamiya K, Takeuchi H. Multidisciplinary team management for prevention of pneumonia and long-term weight loss after esophagectomy: a single-center retrospective study. Esophagus. 2020 Jul;17(3):270-278. doi: 10.1007/s10388-020-00721-0. Epub 2020 Feb 6. PMID 32026048
• 10.23736/S0393-3660.18.03986-4
• Adams SC, Schondorf R, Benoit J, Kilgour RD. Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study. BMC Cancer. 2015 May 18;15:414. doi: 10.1186/s12885-015-1418-3. PMID 25981952

Identifiers

NCT: NCT07671625 · A12/23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗