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Latest on muscle mass loss in cancer and toxicity of treatment

The Journal of Cachexia, Sarcopenia and Muscle published an article titled: “Skeletal muscle mass loss and dose limiting toxicities in metastatic colorectal cancer patients” . 

This latest research shows that muscle mass loss during intensive systemic cancer treatment is associated with dose limiting toxicities.

Dose limiting toxicities are frequent during systemic cancer treatment

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 standard of care for metastatic colorectal cancer patients (mCRC to reduce tumor volume, prolong survival and reduce symptoms. Unfortunately, many patients receiving palliative systemic treatment suffer from dose limiting toxicities (DLT). The consequence of a DLT can be a reduction in dose intensity or dose density, which may reduce the efficacy of systemic treatment.

Two of the risk factors for patients to experience DLT during treatment are malnutrition and low muscle mass at the start of treatment. Recently, the importance of the evolution of muscle mass over time has received more attention. It was shown that systemic treatment has an impact on muscle mass and may cause a decrease in muscle mass during treatment. As a consequence, patients who experience accelerated muscle loss during treatment may be at higher risk of experiencing a DLT.

Sophie Kurk: “Muscle mass loss during systemic treatment increases the risk of experiencing a dose limiting toxicity for metastatic colorectal cancer patients”

In this presented study, Kurk et al. investigated the role of changes in muscle mass over time in experiencing DLTs in mCRC patients receiving two consecutive systemic treatments. Within this homogeneous population of mCRC patients, both low muscle mass at start and a decrease in muscle mass during treatment were significantly associated with an increased risk of DLTs. In contrast, body mass index (BMI) at start and during treatment was not associated with DLTs. These findings support the conclusion that evaluating body composition at the start and during treatment may identify patients at risk of experiencing DLTs.

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 cachexia2. Muscle mass loss and cancer cachexia have a devastating effect on cancer patients’ prognosis and their ability to fully benefit from their treatment, which was shown in this presented study. Skeletal muscle mass has the potential to restore by proper exercise interventions and nutrition. Prospective (randomized) studies are needed to investigate whether an increase in muscle mass may also lead to a reduction in the incidence of DLTs.3,4,5,6 Or alternatively, to prevent overdosing, chemotherapeutic doses could be normalised to muscle mass instead of using a patients’ body surface area (height and weight) which is standard of practice nowadays.

Collaboration
The retrospective analysis of the randomized phase 3 CAIRO37 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 a previous publication8 which showed the potential to gain skeletal muscle mass in mCRC patients, during less intensive systemic regimen or during observation.

 

1.
Online Document GLOBOCAN. Title of subordinate document. In: World Health Organization International Agency for Research on Cancer. Accessed 5 Oct 2017.
2.
Fearon et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 2(5):489-95.
3.
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.
4.
Winter A et al. Normal protein anabolic response to hyperaminoacidemia in insulin-resistant patients with lung cancer cachexia. Clin Nutr 2012;31:765–773.
5.
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.
6.
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.
7.
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.
8.
Kurk et al. Impact of different palliative systemic treatments on skeletal muscle mass in metastatic colorectal cancer patients. JCSM, 2018; 9: 909–919.