However, although the consensus definition and criteria are important developments, it remains that arbitrary definition is not validated by prospective clinical studies. In a recent report, when this definition was applied to patients with stage III non-small-cell lung cancer (NSCLC), 18% of patients were diagnosed with cachexia and another 23% with pre-cachexia.11
Cancer cachexia has a complex multifactorial pathogenesis and is not simply due to reduced nutritional intake. The presence of metastatic tumor inside the body alters normal physiology and metabolism, resulting in a variety of host responses.
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These responses include tumor-induced systemic inflammation, sympathetic activation, hypogonadism, and insulin resistance, which coupled with poor food intake lead to a wasting syndrome characterized by muscle wasting, decline in performance status (PS), poor tolerability to cancer treatment, and eventual death of the patient.12
The key clinical features of cancer cachexia are poor nutritional status, systemic inflammation, and reduced muscle mass. Clinical measures of these features, that is, serum albumin, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), and skeletal muscle index (SMI), are independently associated with poor outcome.13–16
Since cachexia has a complex pathophysiology and affects various organ systems, we wanted to develop a composite index that gives a better estimate of ongoing cachexia as opposed to using a single measure, like weight loss or BMI alone. In the present study, we have incorporated clinical measures of key clinical features of cachexia into a combined index called the cachexia index (CXI) and correlated it with the outcome in patients with advanced NSCLC.
Materials and Methods
Patients. All patients diagnosed with stage IV NSCLC at Louisiana State University Health Science Center between January 1, 2000, and June 30, 2011, were reviewed for this study. Patients were excluded if they had prior history of NSCLC presenting with relapse, prior history of another cancer in the preceding 5 years, and those with incomplete medical information or follow-up.
Following data points were recorded from patient charts: height, weight, absolute neutrophil count, absolute lymphocyte count, and serum albumin either from the date of diagnosis or from the date closest to the diagnosis (within 2 weeks of diagnosis).
Date of progression and radiological response were recorded from charts as judged by the treating physician at that time. We recorded date of death from medical records or obtained it from tumor registry.
We defined progression-free survival (PFS) as the time period from the date of diagnosis to radiological progression, deterioration in PS making patient ineligible for further treatment, or death of the patient. Overall survival (OS) was defined as the time period from date of diagnosis to the date of death (or date of last contact if exact date of death was not available).
Skeletal muscle index. Abdominal computed tomography scan done within 1 month of diagnosis was reviewed to determine the skeletal muscle area (SMA) using MIPAV version 7.0 (Medical Image Processing, Analysis, and Visualization; National Institutes of Health) software at the lumbar spine (L3) level using axial images as described in the literature.15
Abdominal and paraspinal muscles were identified by using boundaries in Hounsfield units set to −29 to +150 and bordered.16,17 SMA was determined by two investigators who were blinded to the patient outcome. Interobserver variation was not calculated. SMI was calculated as SMA/height (m2).
