The effect of radical treatment and rehabilitation on muscle mass and strength: A randomized trial in stages I–III lung cancer patients☆
Introduction
In cancer patients, muscle weakness the result of skeletal muscle wasting (loss of muscle mass) and decreased muscle strength [1] has been associated with increased morbidity [2], [3], excessive fatigue, reduced performance status, lack of energy [4], poor quality of life, poor treatment response and survival [5], [6]. Muscle mass is an even more accurate predictor of survival than BMI [7], [8], [9]. Cancer-related muscle wasting has been attributed to various mechanisms, such as the hypermetabolic status, caused by a direct effect of the tumor-induced secretion of hormones or cytokines [10] on the organism [11] and cancer-related fatigue (CRF) caused by the cancer-treatment and the reduced activity pattern [12]. However, the exact pathophysiological mechanism between muscle wasting, decreased muscle strength and CRF in cancer patients remains poorly understood [13].
Muscle wasting and decreased muscle strength are not systematically addressed in an oncological setting. Peripheral muscle mass and strength are regularly measured in COPD patients, since they are good markers of deconditioning and have been shown to respond to exercise training [8], [9]. Although muscle weakness is mostly observed in patients with advanced lung cancer, some degree may already be present at the time of diagnosis [14]. Little is known about the impact of an oncological treatment on muscle weakness in patients with lung cancer and the impact of a subsequent rehabilitation program. Preliminary data suggest that exercise may slow down the decline in muscle mass and physical functioning [15].
Several methods are available to assess muscle mass: dual energy X-ray absorptiometry (DEXA), midthigh computed tomography (mCT) and bioelectric impedance (BEI). The first two methods are very accurate and yield reproducible results, but are time consuming and expensive [16]. Moreover, mCT requires considerable expertise and exposes the patient to radiation [17], [18]. Conversely, BEI requires limited operator skills, is non-invasive and provides immediate results [16], but is less reliable in underweight or obese patients and in those with abnormal hydration status [19].
Current methods of strength testing include manual muscle testing, computerized dynamometry, and hand-held dynamometry. Although manual muscle testing is a practical option for strength testing, its questionable reliability and subjective nature has created an interest in alternative methods. The use of computerized dynamometry for measurement the isokinetic and isometric muscle strength has been shown to be highly reliable and is currently the gold standard for strength measures. However, their cost makes them uncommon in a clinical setting. Hand-held dynamometry is a relatively inexpensive and portable device, making it a practical alternative to computerized dynamometry. It has been shown to be reliable for evaluation of knee strength in various populations including patients with cancer [20].
The aim of the present study was to investigate the effect of a radical oncological treatment and of a 12-week rehabilitation program on muscle mass and strength in lung cancer patients. Secondary aims were determining the relationship between muscle mass and muscle strength and between muscle mass as measured by mCT and BEI.
Section snippets
Materials and methods
This study is a pre-defined sub study of REINFORCE [21], an open, prospective, randomized, controlled multicenter trial investigating the effects of rehabilitation in patients with either lung cancer or mesothelioma, treated with radical intent. Radical treatment was defined as either complete resection with or without a perioperative platinum-based chemo-(radio) therapy, or definitive thoracic radiotherapy with or without concurrent or sequential platinum-based induction chemotherapy. Patients
Results
Forty-five of the 121 patients included in the REINFORCE study participated in the present sub study (Fig. 1). Seventeen patients left the sub-study between inclusion (M1) and randomization (M2), because of lack of motivation (N = 6), disease progression (N = 5), comorbidities (N = 4) and ineligibility, because treatment did not induce a QF decrease of more than 10% (N = 2). Two patients did not undergo a mCT because of logistic reasons. Of the remaining 26 radically treated patients, 16 patients were
Discussion
The present study shows that muscle mass and muscle strength are significantly reduced in a substantial number of patients with lung cancer at presentation, and are further affected by an oncological treatment with radical intent. Moreover, the present data show that rehabilitation induces a significant recovery of quadriceps mass and strength.
It has been observed that muscle wasting is present in some patients at an early stage of cancer [26]. This study confirms this observation: baseline
Conclusion
The present study shows that a substantial number of lung cancer patients demonstrate a decreased muscle mass and strength at the time of diagnosis. Furthermore, it provides a scientific basis for the use of a structured rehabilitation program in radically treated patients with stages I–III lung cancer. It not only shows that radical treatment exerts negative effect on muscle mass and strength, but unequivocally demonstrates that rehabilitation has the potential to reverse these detrimental
Funding
This study was supported by the Belgian Government Agency of Innovation by Science and Technology for applied Biomedical Research and by the Clinical Research Fund of Ghent University Hospital, Belgium.
Conflict of interest statement
We declare no conflict of interest for all the authors and that the grant provider had no influence on the design and outcome of the study, nor on its analysis or content of this article.
Acknowledgements
The authors thank the members of the pulmonary rehabilitation team, Gilles Thysebaert and the patients for their gracious collaboration.
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Clinical trial number: NCT00752700 .