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Latest research shows muscle mass can be restored after intensive systemic cancer treatment

The Journal of Cachexia, Sarcopenia and Muscle published an article titled: “Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients

Colorectal cancer (CRC) is the third most common malignancy in men and second most common in women1 in the world. Over the past few years, the systemic treatment options for patients with metastatic colorectal cancer have increased. For the majority of these patients, palliative systemic treatment is the standard of care, aiming to reduce tumor related symptoms and to prolong life.

 

Risks of low skeletal muscle mass to treatment

One of the risk factors for adverse events during treatment is the presence of malnutrition. Malnutrition can lead to weight loss and reduced skeletal muscle mass (SMM). The loss of SMM is part of a multifactorial syndrome (cancer cachexia) that has a devastating effect on cancer patient prognosis and their ability to fully benefit from their treatment. Low muscle mass at the start of systemic treatment or muscle mass loss during treatment may lead to chemotherapy-related toxicity, lower quality of life and poor survival in metastatic colorectal cancer patients.

Although systemic treatment likely has an impact on SMM, to date, little is known about the evolution of SMM during consecutive palliative systemic treatments.

Also, SMM loss in cancer patients has been considered an ongoing irreversible process, however, the irreversibility of SMM loss has been challenged in the past2.

Low muscle mass is associated with decreased survival.3–7

Is SMM loss irreversible?

In this published study, Sophie Kurk – University Medical Centre Utrecht (UMCU) – and colleagues show that muscle loss is reversible in mCRC patients receiving systemic treatment. The authors performed a retrospective study of the randomized phase 3 CAIRO3 study8, in which patients received various subsequent palliative systemic treatment regimens, including observation. During CAIRO3 patients were evaluated by CT scans at regular time points for progression of disease. In the presented study, the CT scans were used for the analysis of skeletal muscle mass that allowed to understand the SMM evolution during various consecutive palliative systemic treatment regimens. On average, mCRC patients lost SMM during intensive systemic treatment. Surprisingly, on average, a clear gain of SMM was observed during the following less intensive systemic regimen or during observation. Based on these results the authors conclude that SMM loss is reversible, that it may be influenced by the intensity of systemic regimens and that SMM loss could be a future therapeutic target to improve outcomes of mCRC patients.

Sophie Kurk: “We clearly show that metastatic colorectal cancer patients have the ability to restore muscle mass which was lost during intensive systemic cancer treatment.”

 

Future directions to support muscle mass during treatment

An interesting next step is to do further research on whether or not interventions that aim to improve muscle mass also lead to improved outcome of treatment. For example, nutritional and physical exercise interventions may have the potential to counterbalance SMM loss during high intensive treatment. Additionally, these types of interventions may support potential SMM gain during less intensive treatment.

A recent nutritional intervention study showed a gain in SMM when protein and/or omega 3 fatty acids enriched high energy supplement were added to the diet of non-small cell lung carcinoma patients9–11. In another exercise study during chemotherapy for breast cancer, muscle strength significantly improved in patients randomized to the intervention group.12

Specifically, a multimodal approach combining nutrition and exercise interventions, might be a promising future strategy to prevent SMM loss and subsequent reduced treatment outcomes13, both as supportive care in the adjuvant and palliative setting.

 

Collaboration
The retrospective analysis of the CAIRO3 study is part of a larger project within the Utrecht Centre on Food & Health. The University Medical Centre Utrecht, Utrecht University and Danone Nutricia Research are partners in this collaboration. Through the combined efforts of cancer specialists and academic institutions, the partners aim to better understand the importance of muscle mass evolution during cancer treatment and its impact on outcomes of cancer patients.

1.
Online Document GLOBOCAN. Title of subordinate document. In: World Health Organization International Agency for Research on Cancer. Accesed 5 Oct 2017.
2.
Prado CM, Sawyer MB, Ghosh S, Lieffers JR, Esfandiari N, Antoun S et al. Central tenet of cancer cachexia therapy : do patients with advanced cancer have exploitable anabolic potential? 1–3. Am J Clin Nutr 2013;1012–1019. .
3.
Prado et al, Lancet Oncol 2008 Jul;9(7):629-635.
4.
Martin et al, J Clin Oncol 2013 Apr 20;31(12):1539-47.
5.
Van Vledder et al, Br J Surg 2012 Apr;99(4):550-557 .
6.
Tan et al, Clin Cancer Res 2009 Nov; 15(22)6973-697.
7.
Antoun et al, J Clin Oncol 2010 Feb; 28:1054-1060 .
8.
Simkens LHJ, Van Tinteren H, May A, Ten Tije AJ, Creemers GJM, Loosveld OJL et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): A phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015;385:1843–1852.
9.
Sánchez-lara K, Turcott JG, Juárez-hernández E, Nuñez-valencia C, Villanueva G, Guevara P et al. Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer : Randomised trial q. Clin Nutr 2014;33:1017–1023.
10.
Winter A, MacAdams J, Chevalier S. Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia. Clin Nutr 2012;31:765–773.
11.
Meij BS Van Der, Langius JAE, Smit EF, Spreeuwenberg MD, Blomberg BME Von, Heijboer AC et al. Oral Nutritional Supplements Containing (n-3) Polyunsaturated Fatty Acids Affect the Nutritional Status of Patients with Stage III Non-Small Cell Lung Cancer during. J Nutr 2010;140:1774–1780.
12.
Travier N, Velthuis MJ, Bisschop CNS, Buijs B Van Den, Monninkhof EM, Backx F et al. Effects of an 18-week exercise programme started early during breast cancer treatment : a randomised controlled trial. BMC Med 2015;13:1–11.
13.
Bozzetti F. Forcing the vicious circle: Sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. Ann Oncol 2017;28:2107–2118.