Cancer cachexia is a multifactorial syndrome, primarily defined as a complex metabolic syndrome associated with underlying illness and characterized by loss of muscle.8 Historically, cachexia was thought of as a syndrome of anorexia, fatigue, and weight loss. However, it was recently redefined precisely as lean muscle mass loss associated with chronic illness and/or cancer.9 Using the corrected definition, the prevalence of cachexia was 35.8% in this prospective study. A previous study including patients with several cancer types investigated the association between cachexia and hospitalization costs in the United States, as well as length of stay, and found that the prevalence of cachexia in GC patients was 7.49%,7 much lower than that in our study. It is possible that the previous study did not use the consensus diagnostic criteria for cachexia. Further, ethnic differences may contribute bias to some extent.

The present study prospectively investigated the impact of preoperative cachexia on postoperative OS in GC patients. Our results demonstrated that OS was significantly shorter in patients with preoperative cachexia, and cachexia was found to be an independent risk factor of OS. The relationship between cachexia and disease outcome could probably be explained by the effects of inflammation and malnutrition. Previous studies have suggested a possible association between cachexia and systemic inflammation.10 We found that the NLR and PLR (for which a high value is associated with higher systemic inflammation) were both significantly higher in cachexia patients, in accordance with a study reporting that the preoperative NLR and PLR were useful predictors of postoperative survival in patients with stage I-II GC.11

Cancer cachexia results not only from reduced nutrient intake or availability, but also from metabolic abnormalities triggered by the tumor, as well as by antineoplastic therapies. These factors stimulate systematic inflammation and cytokine networks12 that in turn result in significant loss of body weight, alterations in body composition, and declining physical function. Our findings showed that cachexia patients were more likely to be thinner, with a lower BMI; they also presented with less skeletal muscle, worse muscle function, and worse basic physical condition (higher ASA stage and CCI). Physical condition is a strong prognostic indicator of patient outcomes,13,14 as malnutrition and micronutrient deficiency can lead to the abnormal function of macrophages, neutrophils, and lymphocytes, which can inhibit the immune response,15 decrease response to anticancer therapy,16 and even increase the risk of tumor recurrence.17

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Similar to the results of other studies,7,18 the incidence of cachexia was higher in the elderly group. Considering that cachexia was significantly related to age and both cachexia and age were independent risk factors for OS, age and cachexia may interact with each other. Therefore, we subdivided the patients into four age groups and examined whether the correlation between cachexia and outcome was age-dependent. Interestingly, cachexia was a more effective risk factor for survival in the youngest group (younger than 50 years old; HR =4.947, P=0.029), and it was not significant in the oldest group (older than 70 years old; HR =1.411, P=0.119), which was quite different from the findings of previous studies.6,19 This may be explained by the fact that the interplay between chronic illness and elements such as malnutrition and immobility results in elderly patients being particularly vulnerable to cachexia. Additionally, considering the same diagnostic criteria and their better fundamental physical condition, younger cachexia patients may have better consumption than elderly cachexia patients. Moreover, cachexia only significantly affected postoperative length of stay and hospitalization costs in younger patients.

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This is the first study to focus on cachexia in younger patients, and we found it to be a risk factor for prognosis in that group. We propose that more attention should be paid to improve the cachexia status in younger patients, as it will be more profitable in improving OS and decreasing length and costs of hospitalization. Fortunately, in recent years, data from some intervention studies have shown that cachexia could be potentially managed and reversed by multimodal interventions, including nutrition support, exercise, and drug therapy.20–22

This study has several limitations that should not be overlooked. First, all patients enrolled in our study were treated at two hospitals in Wenzhou, and bias in the population selection may be inevitable. Therefore, a large-scale multicenter trial is essential to verify our conclusion. Additionally, all the patients enrolled were Chinese,

The ethnic differences lead to significant differences in the results from the European and US patients. Second, the follow-up period in the present study is less than 5 years, and complete follow-up data need to be further acquired.

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