Prehabilitation in Pancreatic Surgery

Brief summary public domain (ClinicalTrials.gov)

In patients with pancreatic cancer, older age, multiple comorbidities, frailty, malnutrition and poor functional status are common, especially in individuals receiving neoadjuvant chemotherapy. These characteristics represent potentially modifiable risk factors for poor postoperative outcomes. The goal of this clinical randomized controlled trial is to evaluate the extent to which a four-week multimodal prehabilitation program impacts on postoperative morbidity, functional and nutritional status and health-related quality of life in patients with localized pancreatic or periampullary cancer scheduled for curative surgery. In addition, the impact of prehabilitation on circulating sarcopenia and cancer cachexia biomarkers in PDAC patients will be explored. Included patients will be randomized (ratio 1:1) and allocated either to the intervention group (Multimodal Prehabilitation), which will receive prehabilitation, or to the control group, which will receive no prehabilitation.

Detailed description public domain (ClinicalTrials.gov)

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, with 5-year survival around 10%. The combination of surgical resection and chemotherapy represents the most efficacious therapy to improve prognosis for localized PDAC. Patients with pancreatic cancer are generally older adults in whom frailty, sarcopenia and/or malnutrition are common. These features have all been associated with poor postoperative complications and reduced survival. Therefore, the preoperative period and the time window after the end of chemotherapy constitute a unique opportunity to condition modifiable risk factors, improve functional capacity and address deficiencies in physiologic reserves, which might otherwise preclude surgery or significantly impede recovery. Prehabilitation is defined as the process of enhancing patients' functional capacity to enable them to withstand a stressful event. Multimodal prehabilitation, which defines a program including physical, nutritional, and psychological interventions, has shown the most promising results in gastrointestinal cancer surgery. However, no high-quality evidence is currently available for PDAC patients. STUDY OBJECTIVES: Primary Aim: to evaluate if a 4-week multimodal structured prehabilitation program including physical exercise, nutritional and psychological interventions will result in a clinically significant increase in functional capacity, nutritional status and patient-reported health-related quality of life before surgery when compared to a usual care control group, and evaluate the extent to which multimodal prehabilitation impacts on postoperative morbidity and patient recovery compared to usual care. Secondary Aim: to analyze whether multimodal prehabilitation may impact on the concentration and activity of a panel of specific circulating molecules involved in cancer cachexia and skeletal muscle wasting, chronic inflammation. STUDY DESIGN: A randomized controlled trial will be performed in PDAC and periampullary cancer patients with indication to upfront pancreatic resection or pancreatic resection after completion of neoadjuvant chemotherapy. Included patients will be randomized (ratio 1:1) and allocated either to the intervention group (Multimodal Prehabilitation), which will receive prehabilitation, or to the control group, which will receive no prehabilitation. All patients will receive the same intraoperative and postoperative care based on an established enhanced recovery pathway. …

Intervention public domain (ClinicalTrials.gov)

Other: Multimodal Prehabilitation. Preoperative multimodal intervention including exercise training, nutritional therapy and psychosocial counseling, aimed at preventing or attenuating surgery-driven functional decline. A personalized intervention program will be prescribed based on specific physical, nutritional and psychological conditions recognized during the multimodal assessment. Patients will follow a 2 to 3-day per week exercise program for 4-6 weeks including endurance, resistance, and inspiratory muscle training, tailored to individual preferences and clinical conditions. Based on dietary habits and nutritional status, a certified nutritionist will provide a comprehensive diet management program. A food-based intervention with a balanced macronutrient composition coupled with oral nutritional supplements will be prescribed to achieve the estimated daily energy and protein requirements. Patients will meet with a psychologist to explore their emotional and psychosocial needs related to their current situation.

Arm public domain (ClinicalTrials.gov)

Multimodal Prehabilitation (experimental): The intervention consists of a supervised multimodal prehabilitation program (exercise, nutritional support, and psychosocial counseling) conducted for a minimum of four weeks prior to surgery, during the waiting time following patient enrolment.

Arm public domain (ClinicalTrials.gov)

Usual care (no intervention): Usual preoperative care. Patients in the control group will be treated according to usual care and will be given informative material regarding a healthy lifestyle and how to best prepare for surgery.

Primary outcome public domain (ClinicalTrials.gov)

Comprehensive Complication Index (CCI). Postoperative complications occurring during the index admission or in a subsequent readmission, when related to surgery, will be recorded up to 90 days after surgery and graded by severity using the Dindo-Clavien classification and the Comprehensive Complication index (CCI). The Dindo-Clavien system grades complications according to the therapy needed for treatment: Grade I, are complications that require bedside management; Grade II, are complications that require pharmacologic treatment; Grade III, are complications that require surgical or radiologic intervention and; Grade IV, are complications that require intensive care treatment. Dindo-Clavien Grade III or above are considered severe postoperative complications. The CCI, derived from the Dindo-Clavien system, is a validated metric summarizing the complete spectrum of complications that occurred and their severity in a single score ranging from 0 to 100. Time frame: 90 days after surgery.

Secondary outcome public domain (ClinicalTrials.gov)

Time to patient functional recovery (TFR). Time frame: 90 days after surgery.

Secondary outcome public domain (ClinicalTrials.gov)

Lenght of stay (LOS). Time frame: 90 days after surgery.

Secondary outcome public domain (ClinicalTrials.gov)

Functional capacity. Time frame: One day before surgery; 30 days after surgery; 60 days after surgery; 90 days after surgery.

Secondary outcome public domain (ClinicalTrials.gov)

Nutritional status. Time frame: One day before surgery; 30 days after surgery; 60 days after surgery; 90 days after surgery..

Secondary outcome public domain (ClinicalTrials.gov)

Bioimpedance analysis (BIA) derived body composition. Time frame: One day before surgery; 30 days after surgery; 60 days after surgery; 90 days after surgery.

Secondary outcome public domain (ClinicalTrials.gov)

Computed tomography derived body composition. Time frame: One day before surgery..

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Age ≥ 18 years * Indication for curative resection for pancreatic or periampullary cancer * Signed Informed consent Exclusion Criteria: * Metastatic or unresectable disease found preoperatively * Comorbidities contraindicating prehabilitation regimen (exercise and nutritional intervention) such as orthopedic, cognitive disabilities, chronic renal failure (dialysis or creatinine \>250 mmol) * ASA score 4-5 * Pregnancy * Illiteracy (inability to read and understand Italian language)

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 238 participants (estimated).