POP-UP: a Single-arm, Two-cohort Study: an 8-week Trimodal Pre-habilitation Program for Patients With Pancreatic Ductal Adenocarcinoma and Oesogastric

The success of pre-habilitation is defined by the achievement of the following three criteria:

• At least 75% of the (minimum) planned APA sessions, 6 of 8 sessions with an APA professional and 12 of 16 sessions in autonomy with remote APA supervision (note: the total number of APA sessions can be adapted according to the physical activity level of the patient, with a minimum of 8 supervised sessions and 16 autonomy sessions) and
• Completion of at least 75% of the nutritional evaluations: 6 of 8 planned evaluations and
• Psychological or psychiatric visit before the surgery in function of practice center /resources if a psychological need is shown by Hospital Anxiety and Depression Scale (HADS).

Evaluates completion and adherence of each intervention separately according to predefined success criteria. Unit of Measure: Proportion of patients (%) achieving predefined success criteria

OS defined as time (months) between the date of inclusion and 12 months after surgery

DFS defined as the time (months) between the date inclusion and the date corresponding at 12 months after surgery

HRQoL will be assessed by using the EORTC QLQ-C30 questionnaire at screening, once per month and at the end of intervention visit. The EORTC QLQ-C30 is a cancer specific questionnaire assessing 15 HRQOL scales through 30-items; for each dimension, one score is generated according to the recommendations of the EORTC on a 0-100 scale in order that a high score represents a high functional level, a high Global QoL level, and a high symptomatic level.

The EORTC QLQ-PAN26 is a module specific to pancreatic cancer, to be used in conjunction to the EORTC QLQ-C30. It contains 26 items. As for the EORTC QLQ-C30, one score is generated for each score according to the recommendations of the EORTC on a 0-100 scale in order that a high score represents a high functional level and a high symptomatic level.

The EORTC QLQ-OG25 is a module specific to esophago-gastric cancer to use in conjunction to the EORTC QLQ-C30. It contains 25 items. One score is generated for each score according to the recommendations of the EORTC on a 0-100 scale in order that a high score represents a high functional level and a high symptomatic level

The chemotherapy tolerance with the CTCAE V5.0 (Grade ≥ 3) will be evaluated. Unit of Measure: Number and proportion of patients with Grade ≥3 toxicities (CTCAE v5.0) Toxicities requiring hospitalization, treatment delays, and dose reductions related to toxicity will also be assessed

Major postoperative complications will be measured. Unit of Measure: Number/proportion of patients with Clavien-Dindo Grade ≥3 complications - evaluates serious surgical complications requiring intervention under anesthesia, ICU care, or resulting in death.

The nurse intervention will be evaluated by: Unit of Measure: Number of alerts managed by nurses and oncologists, Weekly remote follow-up completion rate (%), Scheduled vs. completed prehabilitation/posthabilitation sessions (%), and Hospital days

Tracks patient participation in post-habilitation APA sessions and documents reasons for drop-out. Unit of Measure: Number and proportion of patients completing sessions (%). Adherence will also be evaluated using patient-reported outcomes collected through the Activiti® application and APA professional assessments, including the number of APA sessions performed and APA dose intensity.

Fecal elastase and pancreatic enzyme use will be assessed. Unit of Measure: Levels of fecal elastase (µg/g) and pancreatic enzyme consumption (units/day).

Hematologic support and neutropenia will be evaluated. Unit of Measure: G-CSF prescription (yes/no), rate of grade ≥2 neutropenia (%)

Surgical rate will be assessed. Unit of Measure: Number/proportion of patients with surgery

Assessing completion of scheduled perioperative chemotherapy cycles in eligible patients. Unit of Measure: Number/proportion of patients with planned vs received number of perioperative chemotherapy cycles.

Relative dose intensity will be measured. Unit of Measure: Percentage of planned dose received (%)

Evaluating changes in skeletal muscle and fat mass to assess nutritional status during the prehabilitation program. Outcome Measure: Skeletal muscle and adipose tissue areas. Unit of Measure: cm² (cross-sectional area at L3 via TAP-CT or bioimpedance)

Evaluating changes in body weight and BMI to monitor nutritional status. Unit of Measure: kg (weight), kg/m² (BMI).

Measuring dietary intake and eating behavior to assess nutritional status. Unit of Measure: Simple Evaluation of Food Intake (SEFI) visual analog scale. The score is reported using the SEFI visual analog scale, which ranges from 0 to 10, where higher scores indicate better food intake.

Evaluating nutritional status through Serum Albumin evaluation. Unit of Measure: g/L. Meaning: Higher albumin levels indicate better nutritional status and overall protein reserves.

Interpretation:

Good: Higher values (within normal laboratory range) Bad: Lower values (may indicate malnutrition or poor protein intake)

Evaluating inflammatory status through CRP levels. Unit of Measure: mg/L. CRP is a marker of inflammation. Lower CRP indicates lower inflammatory activity.

Interpretation:

Good: Lower values (normal or near-normal, minimal inflammation) Bad: Higher values (indicating active inflammation or possible infection)

Description: Evaluating general health and nutritional status through CBC parameters (e.g., hemoglobin, hematocrit, leukocytes). Unit of Measure: Standard laboratory units (e.g., g/dL for hemoglobin, cells/µL for leukocytes). Meaning: CBC evaluates general health and nutritional status (e.g., hemoglobin for anemia, leukocytes for immune status).

Interpretation:

Good: Values within normal reference ranges Bad: Values outside normal ranges (e.g., low hemoglobin = anemia, abnormal leukocytes = possible infection or immune dysfunction)

Assessing daily physical activity using IPAQ-S. It is a 7-item questionnaire in which duration (hours and minutes per day), frequency (times per week), and intensity (walking, moderate and vigorous) of the previous 7 days will be collected. Sedentary time (self-reported time spent sitting) in the same time period will be recorded (hours/min/day).Unit of Measure: MET-min/week and Minutes/day.

Assessing functional exercise capacity. Outcome Measure: Walking distance (meters).

Assessing upper body muscle strength. Unit of Measure: Kilograms (kg)

Measuring lower limb strength and functional capacity. Unit of Measure: Repetitions per minute

Measuring subjective exertion during functional tests. Unit of Measure: Score. Score on the Borg scale ranges from 6 (no exertion) to 20 (maximal exertion). Lower scores indicate lighter effort (better functional tolerance), higher scores indicate greater perceived exertion (more strain).

Measuring balance and stability. Unit of Measure: Seconds

Measuring mobility and fall risk in older patients. Unit of Measure: Seconds

The HADS is a 14-item questionnaire assessing anxiety through 7 items and depression with 7-items. One score is generated per dimension on a 0-21 scale with the sum of the corresponding items. A score between 0 and 7 represents the absence of anxiety/depression. More of 9 in HADS-anxiety (A) is considered as a presence of an anxiety disorder which needs the intervention of a psychologist (anxiety) and more of 7 in HADS-depression (D) is considered as a presence of depression disorder which needs the intervention of a psychiatrist (depression).

Comparing baseline imaging with preoperative imaging to assess changes in body composition and tumor characteristics, stratified by completion of the prehabilitation program. Unit of Measure: cm² for body composition, mm or cm³ for tumor size

Evaluating differences between baseline diagnostic biopsy and resected surgical specimen for each patient, stratified by completion of the prehabilitation program. Unit of Measure: Pathologic features (categorical or qualitative).