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Accelerated muscle loss precedes progression of disease in cancer patients

The American Journal of Clinical Nutrition published:”Trajectory of body mass and skeletal muscle index and disease progression in metastatic colorectal cancer patients”.

This latest research shows that the speed of muscle mass loss during intensive systemic cancer treatment is associated with disease progression.

Muscle mass loss is common among cancer patients

Colorectal cancer (CRC) is the third most common malignancy in men and second most common in women1 in the world. Palliative systemic treatment is part of the standard care for metastatic colorectal cancer patients (mCRC) to reduce tumor volume, prolong survival and reduce symptoms. During palliative systemic treatment it was previously shown that patients lose muscle mass depending on the treatment intensity2. This loss was calculated by the difference between muscle mass at the start of treatment and muscle mass at the end of the treatment. However, this analysis does not give insight into the linearity of muscle loss and possible associations between the speed of muscle loss (trajectory) and progression of disease (PD).

Sophie Kurk: “Eventually all patients receiving palliative systemic treatment will develop progression of disease. Our data suggest cachexia interventions may already be of value for patients who are responding to
treatment and not necessarily losing SMI at that time.”

In this presented study, Kurk et al. investigated the trajectory of changes in muscle mass over time in mCRC patients receiving two consecutive systemic treatments. By analyzing muscle mass at multiple moments in between two timepoints, it was shown that changes for both body mass index (BMI) and skeletal muscle index (SMI) are not linear and that progression of disease (PD) is preceded by accelerated muscle loss. BMI loss is associated with higher risk of PD, however, the observed weight loss is completely attributed to the loss of muscle.

Future directions to support muscle mass during treatment

During cancer and active cancer treatment, malnutrition, often combined with low physical activity levels, can lead to weight loss, reduced skeletal muscle mass, and eventually to cancer cachexia3.
The presented study shows that serial SMI measurement may have the potential to identify patients who are in an early cachexia phase and of higher risk to experience progression of disease. These patients may benefit from the initiation of cachexia focused interventions including nutritional interventions and physical exercise4,5,6,7,8. Eventually all metastatic patients will experience progression of disease and it is expected that this will be preceded by an accelerated muscle loss. Therefore, early intervention to support muscle mass, also in patients who do not yet show muscle loss, may be of benefit since the non-linear accelerated SMI loss may occur just shortly before progression.

Collaboration

The retrospective analysis of the randomized phase 3 CAIRO39 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. The collaboration resulted in previous publications which showed the potential to gain skeletal muscle mass in mCRC patients2 and the association with dose limiting toxicities10.

1.
Online Document GLOBOCAN. Title of subordinate document. In: World Health Organization International Agency for Research on Cancer. Accessed 5 Oct 2017.
2.
Kurk et al. Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients. JCSM, 2018; 9: 909–919.
3.
Fearon et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 2(5):489-95.
4.
Sánchez-lara 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.
5.
Winter A et al. Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia. Clin Nutr 2012;31:765–773.
6.
Meij BS Van Der 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.
7.
Travier N 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.
8.
Bozzetti F. Forcing the vicious circle: Sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy. Ann Oncol 2017;28:2107–2118.
9.
Simkens 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.
10.
Kurk et al. Skeletal muscle mass loss and dose limiting toxicities in metastatic colorectal cancer patients. JCSM, May 15; Epub ahead of print.