Chemotherapy Toxicities in Nonmetastatic CRC Associated With Low Skeletal Muscle

A review published in ANZ Journal of Surgery found that low skeletal muscle was associated with chemotherapy toxicities in patients who had nonmetastatic colorectal cancer (CRC). However, a more coherent definition of body composition would be needed to confirm the association in other studies.

The leading diagnosis of cancer is CRC, which is the second most common cancer in Australia. Surgical resection and chemotherapy are the top treatments for CRC, but severe toxicity occurs in a significant number of patients who choose chemotherapy. This review aimed to assess correlations between body composition and toxicities related to chemotherapy in patients with nonmetastatic CRC.

Colorectal cancer awareness medical concept | Image credit: Dr_Microbe - stock.adobe.com

Medline, Embase, Cochrane, and Web of Science were searched for studies for this review between January 2011 and January 2023. Studies were included if they had an adult population with a primary diagnosis of nonmetastatic CRC; had CT-assisted body composition assessments; had a study outcome that included chemotherapy toxicity or dose-limiting toxicity; were randomized or nonrandomized control, cohort, and cross-sectional trials; and were published in English. Studies were excluded if the patient had metastatic CRC; palliation was the purpose of the chemotherapy; had body composition measurements not done by CT; were reviews, case reports, autopsy studies, editorials, or conference abstracts; or were published in a language other than English.

There were 6 studies included in this review that took place in Japan, South Korea, the United States, the Netherlands, and Ireland. A collective total of 1417 patients with CRC were included, of which 1024 received chemotherapy and had CTs available.

The toxicity of chemotherapy was measured in 4 studies, whereas dose-limiting toxicity (DLT), which includes dose delay, dose reduction, a change in regimen, incidence of hospitalization, and treatment discontinuations, were evaluated in 5 studies. The toxicities included haemotoxicity, gastrointestinal intoxicity, liver impairment, and neurotoxicity.

There were 4 studies that measured skeletal muscle mass, with 2 using skeletal muscle area (SMA). There were 3 studies that had 94.5% of the participants that reported an increase in chemotherapy toxicities and DLT in patients who had low skeletal muscle mass. Participants in the lowest tertile of SMA had higher odds of treatment cessation done prematurely (OR, 2.34; 95% CI, 1.04-5.24), dose delay (OR, 2.24; 95% CI, 1.37-3.66), and dose reduction (OR, 2.28; 95% CI, 1.19-4.36), according to 1 study that evaluated participants on the FOLFOX regimen. This association remained when the separate components of FOLFOX were individually assessed.

Another study found that decreased skeletal muscle mass led to increased frequency of chemotherapy toxicity. An increased risk of grade 3 and 4 neutropenia was associated with a low PMI (OR, 1.36; 95% CI, 0.93-1.98). This extended to other toxicities, which included anemia, nausea, diarrhea, vomiting, thrombocytopenia, neuropathy, and abnormal liver function (OR, 1.67; 95% CI, 1.13-2.46).

There were some limitations to this study. The 6 studies were heterogeneous in their methods of evaluating body composition as well as many differences in body composition definition. There was also a small sample of studies included, which could limit generalizability in the findings.

The review was able to establish the association between chemotherapy toxicities and skeletal muscle in patients with nonmetastatic CRC.

Reference

Choi CS, Kin K, Cao K, et al. The association of body composition on chemotherapy toxicities in non-metastatic colorectal cancer patients: a systematic review. ANZ J Surg. Published online December 7, 2023. doi:10.1111/ans.18812