The Effect of exeRcise And Diet on Quality of Life in Patients With Incurable Cancer of Esophagus and Stomach (RADICES)

The survival of patients with incurable gastroesophageal cancer can extend over a year with anticancer therapy. However, the number of patients with deteriorating quality of life in this patient group steadily decreases over time during the treatment. Potentially reversible causes related to deterioration of quality of life are diminished muscle mass, physical capacity and nutritional status. Therefore, interventions that can target these in order to maintain or improve quality of life are urgently needed. However, it is yet unknown whether improvement of physical capacity and nutritional status improves quality of life in patients with incurable gastroesophageal adenocarcinoma after failure of first-line treatment. Since these patients are in a precarious situation, the benefits and harms of a combined exercise and nutritional intervention should be carefully evaluated.Therefore this study investigates the effect of a combined exercise and nutrition intervention compared to usual care on quality of life in incurable GAC patients after progression upon first-line treatment. A total of 196 patients with metastasized gastroesophageal cancer will be recruited and randomly allocated 1:1 to standard care or standard care plus a combined exercise and nutritional intervention.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* Incurable adenocarcinoma of the esophagus or stomach
* Recurrence after treatment with curative intent or irresectable/metastatic disease at primary diagnosis. Inclusion can take place regardless of the plan or the actual initiation of multi-line systemic treatment. (i.e. patients that have already started with anticancer therapy are eligible for inclusion too)\*
* Able and willing to perform the exercise and nutritional program and wear the activity tracker.
* Able and willing to fill out the POCOP/RADICES questionnaires.
* Life expectancy \> 12 weeks.
* Age ≥ 18 years.

Exclusion Criteria:

* Unstable bone metastases inducing skeletal fragility as determined by the treating clinician.
* Untreated symptomatic known brain metastasis.
* Serious active infection.
* Too physically active (i.e. \>210 minutes/week of moderate-to-vigorous intentional exercise) or engaging in intense exercise training comparable to the RADICES exercise program.
* Severe neurologic or cardiac impairment according to the American College of Sports Medicine criteria.
* Uncontrolled severe respiratory insufficiency as determined by the treating clinician or if the patient is dependent on oxygen suppletion in rest or during exercise.
* Uncontrolled severe pain.
* Any other contraindications for exercise as determined by the treating physician.
* Any circumstances that would impede adherence to study requirements or ability to give informed consent, as determined by the treating clinician.
* Pregnancy.

  * Note:

After one year of recruitment we broadened our inclusion criteria from GAC patients receiving beyond first-line palliative treatment or best supportive care to any patient with recurrence/progression of GAC after curative treatment or irresectable/metastatic disease at diagnosis, regardless of timing or type of palliative treatment and number of lines received. This was done to increase generalizability and offer the intervention earlier in the palliative phase to enhance its benefits. We acknowledge this results in a more heterogeneous group, but we believe also a more representative group.

The inclusion criterium before broadening was:

Progressive disease after first-line palliative systemic treatment OR within 6 months after completion of curative treatment (i.e. within six months after neoadjuvant chemoradiation, adjuvant nivolumab, or definitive chemoradiation for esophageal adenocarcinoma or within six months after adjuvant 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) for gastric/esophageal cancer or neoadjuvant FLOT if no adjuvant FLOT was given, or after progression during participation in the LyRICX study). Patients on capecitabine monotherapy who are eligible for oxaliplatin reintroduction can be included, too.

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