An analysis of the relationship between metastases and cachexia in lung cancer patients

Abstract

Weight loss and hematogenous metastases are poor prognosis factors in lung cancer patients that can but do not necessarily co‐occur. We retrospectively investigated the clinical association between cachexia, tumor characteristics (such as metastatic burden and mutational status), and treatment in lung cancer patients. The medical records of 394 lung cancer patients from two institutions (Columbia University, USA and Tohoku University, Japan) were reviewed. Information collected included the presence of cachexia, histologic subtype, tumor stage, number of metastases, mutation status, treatment, and survival. Descriptive statistics were performed. Only stage IV patients exhibited >5% weight loss (0.8%, 2.2%, 3.6%, and 5.1%, for stages I to IV; P = 0.0001). Patients with metastases developed cachexia more often than patients without metastases independent of treatment (6.0% and 7.1% weight loss in patients with metastases vs. 2.5% and 2.0% in patients without metastases, before [P = 0.0001] and after [P < 0.0001] treatment, respectively). The change in number of metastatic sites over time correlated with increasing weight loss (5.2%, 10.6%, 13.4%, and 13.4%, for an increase of 0, 1, 2, and ≥3 metastatic sites, from initial diagnosis to the endpoint; P < 0.0001). Patients with cachexia had worse survival than patients without cachexia (hazard ratio, 2.94; 95% confidence interval, 2.08–4.16; P < 0.0001). Tumors with mutated KRAS were associated with an increased risk of weight loss (11.4% weight loss in patients with mutated KRAS vs. 6.0% in patients with wild‐type KRAS; P = 0.0011). Our findings suggest that the capabilities of lung cancer to metastasize and cause cachexia might be linked intrinsically and are independent of treatments administered. KRAS‐mutated tumors were more commonly associated with cachexia.

Peritumoural adipose tissue pro‐inflammatory cytokines are associated with tumoural growth factors in cancer cachexia patients

“…IL‐6 and TNF‐α are important multifunctional cytokines involved in tumour growth and metastasis. A retrospective clinical study of lung cancer patients found a possible link between metastasis and cachexia that was associated with the inherent tumour characteristics …”

Tumour‐derived transforming growth factor‐β signalling contributes to fibrosis in patients with cancer cachexia

“…KRAS mutations are related to drivers linked to aggressiveness in cancer and, consequently, correlate with poor prognosis. A recent study showed that MAPK signalling is constitutively active in KRAS‐mutated colorectal cancer, and other studies have shown that tumours with mutated KRAS were associated with an increased risk of weight loss . Unfortunately, we did not examine tumour genetic profile; hence, we cannot discard an interference of this parameter in our results.…”

“…. On the other hand, several studies show that the presence of cachexia is not directly or exclusively related to greater tumour burden and/or with metastasis; nonetheless, it has been recently shown that metastatic cancer is associated with a higher risk for concomitant cachexia …”

Cancer‐ and Chemotherapy‐Induced Musculoskeletal Degradation

“…The progression of cachexia is exacerbated in the presence of metastasis. For example, in lung cancer patients with metastasis, occurrence of cachexia is higher in metastatic patients than in nonmetastatic patients . As with sarcopenia, cachexia is not limited to those with a BMI <25.…”