Trial Information

Training Effects Following Resection Surgery in Patients With Lung Cancer

Surgical treatment of lung cancer (LC) leads to peripheral and respiratory muscle
dysfunction (Mdys) with exercise limitation. This characteristic feature might be generated,
not only for a reduced lung function, but also by deconditioning as well as respiratory and
peripheral muscle dysfunction. It remains unknown the potential benefits resulting from a
specific training and its effects on plasmatic mediators.

Chronic diseases are the leading cause of morbidity and mortality worldwide and is known
that regular exercise has a beneficial effect on most of them. Many studies have shown the
benefit of exercise in patients diagnosed with cancer, especially breast and colorectal
cancer, even during active phases of specific treatment, however few studies refers to
possible benefit of exercise in patients with lung cancer following surgical resection. Lung
cancer is one of the most common cancers in Spain, the second in the general population and
the first if we refer exclusively to the male population. Not only it is a common type of
cancer, but also presents a high mortality with a survival rate at 5 years of approximately
12%. However, survival improves significantly in stage I (60-80% at 5 years) and
progressively worse until stage IV (<5% at 5 years). Surgery is the treatment of choice for
lung cancer in stages I and IIa. Despite the good results in terms of survival, it is not
free of side effects. Depending on the extent of lung resection, it may result in functional
limitations and impact on the patients' quality of life. Pulmonary lobectomy entails a
significant reduction of the functional reserve: impaired lung function (FEV1 of 15%) and
reduced exercise capacity (16% in the shuttle test). In contrast, in the pneumonectomy,
reduced pulmonary function is disproportionately higher (FEV1 of 35%) in comparison with the
exercise limitation (23%). To date we have no knowledge of studies that have specifically
evaluated the effects of exercise training in these patients.

Dysfunction of the diaphragm and other respiratory muscles, prevalent in COPD (chronic
obstructive pulmonary disease) patients, has important clinical implications. It associates
with susceptibility to hypercapnic ventilatory failure, ineffective cough, and even higher
incidence of repeated hospital admissions and mortality. Therefore, respiratory muscle
weakness described in some patients justifies the need to train respiratory muscles because
there is no general exercise (bicycle, legs, arms) able to induce an overload enough to
achieve training effect on respiratory muscles. Since a large proportion of lung cancer
patients also suffer from COPD, endurance and strength of respiratory muscles are expected
to be reduced. Moreover, after lobectomy patients have some degree of peripheral muscle
deconditioning, which could be linked to the loss of reserve function, but also the relative
rest. Although muscle training has been successfully used to restore function in patients
with various chronic diseases and frailty, there is little evidence on the beneficial
effects of muscle training in patients after lung cancer surgery.

Many studies have related the insulin-like growth factor I (IGF-I) and its major regulatory
proteins, Insulin-like growth factor binding protein (IGFBP-3) with various malignancies,
including lung cancer. In healthy subjects with sedentary lifestyle, caloric diet leads to
obesity and alterations of hormonal, metabolic and inflammatory modulate carcinogenesis.
These disorders include chronic hyperinsulinemia, elevated plasma IGF-I, plasma enhanced
bioavailability and increased steroid sex hormones of systemic inflammation markers.
Physical exercise, in addition to its cardiovascular effects and/or muscular strength and
endurance produces a response on plasmatic levels of IGF-I and IGFBP-3. This variability has
been justified, in most cases, depending on type, intensity and/or duration of the exercise
performed.