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

Обзор

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.

Подробное описание

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. Accordingly, we had to alter stratification. The first 23 patients were stratified by: duration of first-line therapy (shorter or longer than 6 months), WHO performance status (0, 1, 2), and intended start of second-line systemic therapy (yes or no). After broadening the criteria, stratification factors were changed to: WHO performance status (0 versus ≥1) and treatment line (first versus second/higher/best supportive care).

Due to the nature of the intervention, it is not possible to blind the patients, the local study nurses, or the investigators to the treatment assignment.

Вмешательства

• Другое Exercise intervention
  During 12 weeks, patients will visit twice a week a trained oncology physiotherapist for one hour per session. This training includes supervised aerobic and resistance exercises to increase aerobic condition and muscle resistance, based on their own fitness level as assessed at baseline. Additionally, physiotherapists will educate participants on how to increase their daily activity. To this end, all participants will receive an activity tracker to monitor their daily activities.
• Другое Nutrition intervention
  Once every two weeks patients in the intervention group will receive a nutritional assessment and intervention by a trained dietician for optimization of their nutritional intake to improve their nutritional status, following the ESPEN guideline on nutrition in cancer patients and the national guidelines of the National Nutritionists Oncology Working Group (NNOWG; in Dutch: Landelijke Werkgroep Diëtisten Oncologie, LWDO). Moreover, an amount of 15-25 grams of protein within 1-2 hours after exerc

Первичные конечные точки

• Quality of life (EORTC-QLQ-30) summary score [Срок оценки: Baseline, 6 weeks and every 12 weeks up to one year after intervention]

Вторичные конечные точки (12)

• Aerobic capacity: MSEC [Срок оценки: Baseline, 12 weeks]
• Muscle strength: Hand grip strength [Срок оценки: Baseline, 12 weeks]
• Body composition: Muscle mass [Срок оценки: Baseline, 12 weeks]
• Body composition: Fat mass [Срок оценки: Baseline, 12 weeks]
• Body composition: Weight [Срок оценки: Baseline, 12 weeks]
• Self-reported screening of malnutrition [Срок оценки: Baseline and every 12 weeks up to one year after intervention]
• Physical activity [Срок оценки: Baseline, 12 weeks]
• WHO performance status [Срок оценки: Baseline and during the intervention, until the end of the intervention (12 weeks).]
• Quality of life (EORTC-QLQ-30) total score [Срок оценки: Baseline, 6 weeks and every 12 weeks up to one year after intervention]
• Self-reported screening of sarcopenia [Срок оценки: Baseline,12 weeks]
• Skeletal muscle index [Срок оценки: Baseline, 12 weeks.]
• Muscle strength: leg press maximal muscle strength [Срок оценки: Baseline, 12 weeks]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Поддерживающая терапия

Центры проведения

Нидерланды · 22 центра

• Amsterdam UMC — Amsterdam
• UMC Utrecht — Utrecht
• Jeroen Bosch Hospital — 's-Hertogenbosch
• Flevoziekenhuis — Almere Stad
• Meander Medical Center — Amersfoort
• Reinier de Graaf — Delft
• Catharina Ziekenhuis — Eindhoven
• Beatrix Hospital — Gorinchem
• … и ещё 14 центров

Публикации

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• van Vulpen JK, Siersema PD, van Hillegersberg R, Nieuwenhuijzen GAP, Kouwenhoven EA, Groenendijk RPR, van der Peet DL, Hazebroek EJ, Rosman C, Schippers CCG, Steenhagen E, Peeters PHM, May AM. Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized controlled trial. BMC Cancer. 2017 Aug 18;17(1):552. doi: 10.1186/s12885-017-3542-8. PMID 28821284
• Hiensch AE, Monninkhof EM, Schmidt ME, Zopf EM, Bolam KA, Aaronson NK, Belloso J, Bloch W, Clauss D, Depenbusch J, Lachowicz M, Pelaez M, Rundqvist H, Senkus E, Stuiver MM, Trevaskis M, Urruticoechea A, Rosenberger F, van der Wall E, de Wit GA, Zimmer P, Wengstrom Y, Steindorf K, May AM. Design of a multinational randomized controlled trial to assess the effects of structured and individualized ex PMID 35906659
• Arends J, Bachmann P, Baracos V, Barthelemy N, Bertz H, Bozzetti F, Fearon K, Hutterer E, Isenring E, Kaasa S, Krznaric Z, Laird B, Larsson M, Laviano A, Muhlebach S, Muscaritoli M, Oldervoll L, Ravasco P, Solheim T, Strasser F, de van der Schueren M, Preiser JC. ESPEN guidelines on nutrition in cancer patients. Clin Nutr. 2017 Feb;36(1):11-48. doi: 10.1016/j.clnu.2016.07.015. Epub 2016 Aug 6. PMID 27637832
• Campbell KL, Winters-Stone KM, Wiskemann J, May AM, Schwartz AL, Courneya KS, Zucker DS, Matthews CE, Ligibel JA, Gerber LH, Morris GS, Patel AV, Hue TF, Perna FM, Schmitz KH. Exercise Guidelines for Cancer Survivors: Consensus Statement from International Multidisciplinary Roundtable. Med Sci Sports Exerc. 2019 Nov;51(11):2375-2390. doi: 10.1249/MSS.0000000000002116. PMID 31626055
• Giesinger JM, Kieffer JM, Fayers PM, Groenvold M, Petersen MA, Scott NW, Sprangers MA, Velikova G, Aaronson NK; EORTC Quality of Life Group. Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust. J Clin Epidemiol. 2016 Jan;69:79-88. doi: 10.1016/j.jclinepi.2015.08.007. Epub 2015 Sep 28. PMID 26327487
• Ligibel JA, Bohlke K, May AM, Clinton SK, Demark-Wahnefried W, Gilchrist SC, Irwin ML, Late M, Mansfield S, Marshall TF, Meyerhardt JA, Thomson CA, Wood WA, Alfano CM. Exercise, Diet, and Weight Management During Cancer Treatment: ASCO Guideline. J Clin Oncol. 2022 Aug 1;40(22):2491-2507. doi: 10.1200/JCO.22.00687. Epub 2022 May 16. PMID 35576506
• Bonhof A, Hiensch AE, Wierdsma NJ, Huis In 't Veld LF, Bakker SD, Beeker A, Davidis-van Schoonhoven M, Droogendijk H, Drooger JC, Douma JAJ, Goedegebuure RSA, Haj Mohammad N, van Hellemond IEG, Herbschleb K, Janssen JJB, Mostert B, Slingerland M, Sommeijer D, Timmermans L, Verschoor AJ, de Weger VA, Westdorp H, Wumkes ML, May AM, van Laarhoven HWM. Effects of exercise and diet in patients with inc PMID 41592243

Идентификаторы

NCT: NCT06138223 · NL83835.018.23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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