Cancer cachexia remains a challenging condition affecting many cancer patients, especially those with advanced disease. Identifying mechanism and treatment of cancer cachexia is one of the provocative questions recently put forward by the National Cancer Institute (NCI).

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Currently, there are no Food and Drug Administration-approved treatments for cancer cachexia (http://provocativequestions.nci.nih.gov/archived-rfas-and-pqs/rfa-archive-2012/mainquestions_listview?mqCategory=Group+D). One of the current challenges in managing cancer cachexia is to reliably identify it at the onset and estimate the degree of cachexia.

The current consensus definition of cancer cachexia (weight loss >5%) is based on the degree of weight loss prior to diagnosis.5 What is not known is whether this degree of weight loss also correlates with ability to receive cancer treatment or with overall outcome.

Moreover, a definition of cancer cachexia based on weight loss alone may be a good way of screening patients for cancer cachexia, but it does not take into account muscle wasting (sarcopenia) or nutritional status of the patient. 

Table III – Univariate and multivariate analysis of clinical characteristics on PFS and OS in patients with metastatic non-small-cell lung cancer Univariate analysis.
Variable PFS HR P OS HR P
F/M 1.24 (0.85–1.83) 0.2662 1.08 (0.72–1.62) 0.6939
AA/W 0.885 (0.607–1.290) 0.5251 0.95 (0.65–1.38) 0.8016
PS 0–1/2–4 0.464 (0.272–0.792) 0.0048* 0.41 (0.21–0.79) 0.0081*
Adeno/No 0.883 (0.613–1.274) 0.5067 0.94 (0.65–1.37) 0.7704
No Chemo 2.815 (1.462–5.419) 0.0020* 3.12 (1.75–5.56) 0.0001*
SMI (<40) 1.665 (1.042–2.660) 0.033* 1.36 (0.94–1.96) 0.1
NLR ≤5 0.47 (0.29–0.75) 0.001* 0.6 (0.41–0.90) 0.018*
Alb <3 2.03 (1.26–3.41) 0.004* 1.9 (1.22–3.13) 0.0048*
CXI <35 2.432 (1.522–3.885) 0.0002* 2.08 (1.38–3.12) 0.0005*
Age (<60 years) 0.92 (0.75–1.13) 0.4270 0.819 (0.67–0.998) 0.0475
PS 0–1 0.51 (0.32–0.83) 0.0053* 0.44 (0.27–0.71) 0.0008*
No chemo 2.83 (1.76–4.54) <0.0001* 3.26 (2.02–5.26) <0.0001*
Stage II cachexia (CXI <35) 1.94 (1.27–2.95) 0.0022* 1.53 (1.009–2.34) 0.0459*
Notes: *Statistically significant. Multivariate analysis adjusting for sex, race, and histology.
Abbreviations: F/M, female/male; AA/W, African American/White; PS, performance status; adeno, adenocarcinoma; SMI, skeletal muscle index; NLR, neutrophil-tolymphocyte ratio; Alb, serum albumin; CXI, cachexia index; PFS, progression-free survival; OS, overall survival.

In the current study, we reviewed patients newly diagnosed with advanced NSCLC at our institution over a 10-year period. Because sarcopenia is a hallmark of cancer cachexia, we estimated SMI at L3 level using the method described above. Because cancer cachexia is also characterized by systemic inflammation and poor nutritional status, we estimated the degree of systemic inflammation using the NLR (for which a high value is associated with higher systemic inflammation) and nutritional status with serum albumin.

In order to estimate the degree of cancer cachexia, we developed a composite index that incorporates features of sarcopenia, systemic inflammation, and nutritional status into a combined index called the CXI. Patients were divided around the median into stage I (CXI ≥35) and stage II (<35) cachexia.

Patients with stage II cachexia are deemed to have advanced cachexia than those with stage I since low CXI is associated with lower SMI, lower albumin, and higher NLR. Patients with stage II cachexia were more likely to have more than two sites of metastatic disease and PS of ≥2.

They were also less likely to receive chemotherapy and have a poor response to it. The PFS and OS were significantly shorter for these patients than for those with stage I cachexia (Table 2). Dichotomization of a continuous variable though often discouraged is a common practice in medical literature, for example, hypertension >140/90 or BMI >30.