PeRioperative Study of Exercise Training - a None-randomized Feasibility Study: Usual Care Observation vs Exercise Training Intervention in Patients With Operable Cancer of the Gastroesophageal Junction

BACKGROUND AND RATIONALE Patients diagnosed with operable cancer in upper gastro-intestinal (GI) tract undergo serious therapeutic procedures including invasive surgery combined with chemo- or chemo-radio therapy before (neo-adjuvant) and/or after (adjuvant) surgery. Despite recent advances, especially in surgical techniques and patient care follow-up, the population is faced with one of the worst prognosis for patients with operable staged disease, with a 5-year relative survival of 35-40%. The only possibility of long-term survival is positive surgical outcome, which includes the surgical principle of performing wide clearance, achieving a negative margin (R0 resection), and performing a radical lymphadenectomy. To this end, considerable efforts have been made in recent years optimizing the perioperative period in order to provide the patients and the surgeons with the best possible chances of achieving this surgical outcome.

Adenocarcinoma of the gastro-esophageal junction (GEJ) has increased in incidence over the last quarter century. For patients presenting with localized disease, advances in standards of care have emerged in recent years which have improved disease management. Firstly, comprehensive staging with Computed Tomography (CT), endoscopic ultrasound, diagnostic laparoscopy and fluoro deoxy glucose position emission tomography (18FDG-PET) permits exclusion of patients for curative therapy who might previously have been scheduled for resection. Secondly, evidence supports that esophagectomy is performed in high-volume hospitals by high-volume surgeons. Finally, standard neoadjuvant and adjuvant therapies are performed in most centers for patients with localized esophageal adenocarcinoma which has improved both short- and long-term cancer outcomes.

Prognostic role of Muscle Function in upper GI cancer For all upper GI cancers, including GEJ, the perioperative course of therapy is associated with severe deconditioning which includes weight loss and poor physical function. Over the last decade, strong observational evidence has emerged supporting that poor pre-surgical muscle function, defined as either low muscle mass/area (sarcopenia) or low functional strength, is a strong independent predictor of post-surgical outcomes including mortality, surgical complications and chemotherapy dose-reduction. Importantly, strong evidence across different malignancies has shown that the prognostic value of muscle function is independent from body mass, and may actually be under-reported due to sarcopenic obesity. Thus, current available therapeutic countermeasures in clinical practice, which exclusively involve nutritional interventions, may have limited potential for ameliorating the progressive muscle dysfunction during perioperative treatment for GEJ cancer.

Exercise-Oncology and Upper GI cancer Epidemiological evidence across both heterogeneous and homogeneous groups of cancer patients have shown that low physical activity level after diagnosis is associated with poor disease-specific and overall survival. Despite a general emerging interest, limited attention has been dedicated to the exploration of safety, feasibility and efficacy of structured exercise interventions in patients with upper GI cancer. However, data from recent studies suggests an unmet potential of physical exercise in these patients, with particular emphasis on the pre-surgical period.

STUDY OBJECTIVES Primary Objective