Elsevier

Clinical Nutrition

Volume 39, Issue 2, February 2020, Pages 501-509
Clinical Nutrition

Original article
Low muscle mass is associated with early termination of chemotherapy related to toxicity in patients with head and neck cancer

https://doi.org/10.1016/j.clnu.2019.02.029Get rights and content

Summary

Background & aims

We studied whether low pre-treatment muscle mass, measured with CT at thoracic (T4) or lumbar level (L3) associates with early termination of chemotherapy related to toxicity in head and neck cancer (HNC) patients.

Methods

This was a retrospective chart and image review. Adult HNC patients treated with (surgery and) platinum-based chemo-radiotherapy were included if a pre-treatment CT scan at T4 or L3 level was available. Muscle mass was evaluated by assessment of skeletal muscle index (SMI; cm2/m2). T4 and L3 SMI measurements were corrected for deviation from their respective means and were merged into one score for SMI difference (cm2/m2). All cases were assessed for presence of toxicity-related unplanned early termination of chemotherapy (‘early termination’). Univariate and multivariate logistic regression models were used to investigate associations between pooled SMI and early termination.

Results

213 patients (age: 57.9 ± 10.3 y, male: 77%, T4 image: 45%) were included. A significant association between SMI as a continuous variable and early termination was found, both in the univariate analysis (p = 0.007, OR = 0.96 [0.94–0.99]) and the multivariate analysis (p = 0.021, OR 0.96 [0.92–0.99]). The multivariate models identified potential associations with type of chemotherapy, presence of co-morbidity, a combination of (former) smoking and alcohol consumption, and sex.

Conclusion

Lower muscle mass was robustly associated with higher odds of early termination of chemotherapy in HNC patients. Further prospective studies are required to tailor the care for patients with low muscle mass and to avoid early termination of chemotherapy.

Introduction

Decreased oral intake due to tumor location cancer treatment, and/or cachexia is common in patients with head and neck cancer (HNC) and may induce loss of skeletal muscle [1], [2], [3], [4]. In turn, low muscle mass has a negative impact on overall function and survival in patients with HNC [5], [6], [7], [8], [9]. However, the treatment approach in patients with locally advanced HNC can be aggressive and may consist of surgery followed by radiotherapy, with or without concomitant chemotherapy. In patients not eligible for surgery or when the anticipated functional outcome with surgery is poor, radiotherapy with concomitant chemotherapy is preferred [10], [11], [12]. Although prognosis improves when patients are capable of completing their therapy, early termination of treatment related to toxicity is observed more often in cancer patients with low muscle mass, and thus such benefit may be limited [7], [13], [14].

The development of chemotherapy toxicity may be partially explained by variation in body composition in patients with cancer [15]. The overall weight is comprised mostly of fat tissue and non-fat tissue. In turn, non-fat tissue is comprised of bone tissue and lean tissue such as organ tissues (e.g., liver and kidneys) and muscle tissue [16], [17]. Distribution and metabolism of water soluble chemotherapy agents, such as cisplatin, mainly takes place in the lean tissue [18]. Therefore, patients with low muscle mass may have a smaller amount of area available for distribution of chemotherapy agents due the limited amount of lean tissue. Recent studies have revealed there is considerable variation in the proportions of lean and fat tissues in patients with cancer, and patients with solid tumors may present as overweight or obese, while simultaneously showing severe loss of skeletal muscle mass [8], [13], [19]. Body area estimates based on body mass and stature are used for dose calculation of chemotherapy agents such as cisplatin [20]. Thus, if a chemotherapy agent distributes well in lean tissue, patients with relatively low muscle mass may be at risk of receiving a higher dose of chemotherapy agent relative to the actual amount of lean tissue, due to overestimation of lean tissue. This relatively high dose of chemotherapy may increase risk of chemotherapy toxicity [7], [14], [17], [21].

Chemotherapy toxicity may result in early termination of chemotherapy [22]. Accurate identification of patients with low muscle mass is currently possible, since muscle mass has become identifiable and quantifiable with image-based approaches, such as computed tomography (CT). CT analysis of the lumbar muscle area has been thoroughly validated for the evaluation of human body composition and correlates well with lean body mass [23], [24], [25]. In some patient populations, CT images of the lumbar muscle area are not generally available, and CT analysis of thoracic muscle area may serve as an alternative [26]. However, although it is now possible to accurately identify patients with low muscle mass, it is still unclear to what extent toxicity of chemotherapy treatment correlates with muscle area identified with lumbar or thoracic CT cross-sections in HNC patients. Therefore, we aimed to study whether low pre-treatment lumbar or thoracic muscle area as measured with CT is associated with toxicity-related early termination of chemotherapy treatment, in patients with HNC treated with concomitant radiotherapy and chemotherapy.

Section snippets

Patients and study design

This study was conducted in accordance with the Declaration of Helsinki and approved by the institutional research ethics board. Data were collected in consecutive adult patients diagnosed with HNC during their initial visit to the outpatient medical oncology clinic at the tertiary cancer treatment center serving northern Alberta. Demographic information, and cancer site and stage were obtained from the Alberta Cancer Registry, certified by the North American Association for Central Cancer

Results

In total, 213 patients met the inclusion criteria and could be included in the analysis (Sample I: n = 93; Sample II: n = 120). Characteristics of the included HNC patients prior to CRT are reported in Table 1. All patients received at least one cycle of chemotherapy. Of these 213 patients, 61 (29%) terminated chemotherapy prematurely. In one patient that terminated chemotherapy early, the initial chemotherapy treatment plan was altered from cisplatin to carboplatin. In 28 patients, the initial

Discussion

The results of our study indicate that cross-sectional measurements of large and representative muscle areas are significantly associated with incidence of toxicity-related early termination of chemotherapy in patients with HNC. A lower level of lumbar and thoracic SMI of 1 cm2/m2 was firmly associated with 4–5% higher odds of early termination of chemotherapy. Conversely, a higher level of lumbar and thoracic SMI of 1 cm2/m2 was firmly associated with 4–5% lower odds of early termination of

Conflicts of interest

M.J. Sealy: none declared.

T. Dechaphunkul: none declared.

C.P. van der Schans: none declared.

W.P. Krijnen: none declared.

J.L.N. Roodenburg: none declared.

J. Walker: none declared.

H. Jager-Wittenaar: none declared.

V.E. Baracos: consultancy for Pfizer.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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