Our research showed a comprehensive analysis from clinicopathological data and CT scans to explore the survival outcomes in the Chinese population with GIST following surgery. Preoperative sarcopenia defined by SMI was associated with poor survival. CT has a high degree of validity in assessing body composition and is regarded as the gold standard method for estimating muscle [10, 14, 15].To the best of our knowledge, this is the first research indicating that impaired effects of sarcopenia for the survival in patients with GIST worldwide.
Sarcopenia is a syndrome affecting innumerable people with cancers and is independent predictor of detrimental outcomes such as physical disability, poor quality of life, and reduced survival. Sarcopenia is considered a significant constituent of cancer cachexia syndrome, and the pathophysiology is involved with the systemic inflammation, including anabolic and catabolic pathways. Proinflammatory cytokine such as cytokines tumor necrosis factor (TNF-α), interleukins (ILs) regulate the anabolic pathways via lipid mobilization and protein catabolism. These cytokines could also inhibit myocyte differentiation and mediate the atrophy in skeletal muscle through SMAD2/3 signaling. What’s worse, the loss of skeletal muscle could further cause local inflammation, contributing to increasing systemic inflammation. Some studies demonstrated association between skeletal muscle mass and systemic inflammatory markers in many cancers[20-23]. These correlations provide the solid basis of inflammation mechanism responsible for sarcopenia.
However, the clinical definition of SMI remains inconclusive, the most widely used definitions were defined by Prado in the western people. However, these definitions might not be applicable to Chinese GIST patients because BMI and physique differs greatly between eastern and western populations. Therefore, we used optimum stratification analysis to define the SMI cutoff. The incidence of sarcopenia with GIST patients was 26.2 % (28/107) in our study is consistent with the previous study  with sarcopenic morbidity of 38.7% in the GIST patients.
Sarcopenic patients represented lower BMI and serum albumin. These two factors were associated with sarcopenia but not with the survival. Sarcopenia is considered to be a better predictive tool than BMI and albumin for survival. BMI is not available to evaluate the body composition. Sarcopenic obesity may mislead clinical decision concerning nutritional treatment because sarcopenia could exist in the normal and overweight patients with elevated BMI. Albumin is a negative acute-phase protein that decreases in concentration with ongoing systemic inflammation, poor health, and malnutrition which lead to the decreased skeletal muscle mass, hence, lower albumin might be associated with low-SMI value to reflect the sarcopenic condition. This study is conformable with previous findings in other cancers[25, 26].
The high efficient predictive tool is indispensable for GIST patients. At present, a few influential predictive models for the prognosis of GIST have been designed. Miettinen proposed that tumor size, mitotic rate, and tumor site can accurately predict the risk of GIST patients. Gold developed a nomogram for the recurrence free survival of patients with GIST patients after complete resections. This study established a new nomogram including resection style, mitotic index and sarcopenia. To prove the clinical validity, we evaluated whether the nomogram-assisted decisions would be beneficial to patient outcomes or not. The novel method of decision curve analysis demonstrated that if the threshold probability of a patient or doctor is 40%, then probably 7.5 persons would benefit without detriment of others. Our nomogram also represented the reliable performance with high c-index of 0.794. Our nomogram did not include other important clinical factors, for instance, the tumor size, tumor site and presence of rupture which have been reported to be correlated with the mortality of GIST patients[27-29]. The possible reason might be some patient records affecting the data bias was excluded for insufficient clinical data. In the future study, we need the more clinical samples and validation set to prove our nomogram.
To reinforce the precision of tumor biological behavior prediction by only depending on resection style and mitotic counts, we integrated the new parameter sarcopenia by measurement of SMI into our nomogram. Preoperative and postoperative SMI are of equal importance. An interesting study showed 63.6% of initially sarcopenic GIST patients became non-sarcopenic after 6 months of imatinib. This reversal might be explained by the drug’s anti-tumor activity. Hence, clinicians should persist in nutritional guidance for the whole management of GIST patients. Meanwhile, patients are encouraged to exercise and receive appropriate nutritional treatment for muscle protein synthesis against sarcopenia[11, 30].
This study had several limitations. First, according to the European Working Group on Sarcopenia in Older People (EWGSOP), sarcopenia should be measured by the parameters of muscle mass, muscle strength and physical performance. We regarded only muscle mass as the definition of sarcopenia due to the retrospective design, and prospective study is further needed including more assessment tools for sarcopenia. Second, merely 107 patients were enrolled due to insufficient available clinical data and low incidence of GIST. Third, this was a single-institution study of small sample, and whether the results are feasible for other patient sets which needs further internal and external validation. Nevertheless, to best of our acknowledgement, this is the first study to establish a predicting model based on the preoperative sarcopenia of GISTs patients. More variables, for instance, inflammation index and gene detection could be incorporated in future.