From a practical point of view, dichotomization around median would help clinicians use the index to categorize and explain the risk of progression or dying when the median value is compared. Because men and women have different muscle mass, we also determined whether the CXI correlates with outcome in men and women separately. Patients with stage II cachexia had worse PFS and OS independent of the gender (Table 4) (P < 0.001).
|Table IV – PFS and OS of patients with stage I and stage II cachexia based on gender.|
|Gender||Stage I Cachexia
|Stage II Cachexia
|N = 111||M(N = 40) F(N = 16)||M(N = 37) F(N = 18)|
|PFS||5.49 4.75||2.45 2.18||<0.001*|
|OS||8.88 7.88||3.27 4.62||<0.001*|
|Notes: *Statistically significant, one observation with invalid time, strata, or censoring was deleted.
Abbreviations: PFS, progression-free survival; OS, overall survival; CXI, cachexia index.
On univariate analysis PS >2, not receiving chemotherapy, serum albumin, NLR, and CXI ≤35 correlated with poor PFS and OS. On multivariate analysis adjusting for race, gender, and histology, CXI was independently associated with worse PFS and OS. Thus, patients with CXI of ≤35 were 53% more likely to die earlier from NSCLC than patients with CXI >35.
In our study, weight loss >5% (current clinical consensus definition) and BMI <20 alone did not correlate with poor outcome. This may be due to less accurate estimate and reporting of weight loss in a retrospective review. Also in the era of endemic obesity, sometimes BMI may not be a good estimate of muscle wasting as seen in patients with cachexia.
We had previously shown using advanced lung cancer inflammation index (ALI) that when BMI is combined with serum albumin and NLR, patients with advanced NSCLC can be divided into good and poor prognosis.18
CXI is an improvement on ALI as CXI incorporates SMI that is a hallmark of cancer cachexia. If SMI is not readily available, ALI can be used to identify patients with high inflammation and risk of early progression.
Cancer cachexia manifests as a spectrum divided into pre-cachexia, cachexia, and refractory cachexia, but the distinction between these stages can be difficult. Others have also attempted to quantify or stage cachexia by developing tools like inflammatory-nutritional index (based on CRP and serum albumin)19 and cachexia score (needs validation in patient population).20
Click here to enlarge Figure 2
However, it is not known if these correlate with patient outcome also. Another important score described in the literature is Glasgow prognostic score (based on CRP and serum albumin). This has been shown to be correlated with outcome in cancer patients but does not take into account muscle wasting that is a hallmark of cancer cachexia.21
More recently, Kasymjanova et al has proposed an inflammatory score based on CRP and total white blood cell count as a prognostic marker in patients with advanced NSCLC. The score is able to predict response to chemotherapy as well as outcome. This score is based only on inflammatory parameters and does not take into account measures like BMI or muscle mass.22
Gagnon et al has also proposed a five-point Montreal prognostic score as a way of estimating survival in patients with advanced NSCLC. This score also incorporates two cancer stages (stage III vs IV) in estimating the outcome, which in our opinion is a limitation of this score as stage III and IV lung cancers have a very different natural history, treatment, and outcome.23
CXI has been developed using a uniform patient population, that is, all patients were newly diagnosed with stage IV NSCLC. None of the patients had received any treatment to account for weight loss or poor nutritional status. CXI is a composite index that takes into account key features of cancer cachexia, that is, sarcopenia, systemic inflammation, and serum albumin.